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Animal viruses have their genetic material copied by a host cell after which they are released into the environment to cause disease.
- Describe various animal viruses and the diseases they cause
- Animal viruses may enter a host cell by either receptor -mediated endocytosis or by changing shape and entering the cell through the cell membrane.
- Viruses cause diseases in humans and other animals; they often have to run their course before symptoms disappear.
- Examples of viral animal diseases include hepatitis C, chicken pox, and shingles.
- receptor-mediated endocytosis: a process by which cells internalize molecules (endocytosis) by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized
Animal viruses, unlike the viruses of plants and bacteria, do not have to penetrate a cell wall to gain access to the host cell. Non-enveloped or “naked” animal viruses may enter cells in two different ways. When a protein in the viral capsid binds to its receptor on the host cell, the virus may be taken inside the cell via a vesicle during the normal cell process of receptor-mediated endocytosis. An alternative method of cell penetration used by non-enveloped viruses is for capsid proteins to undergo shape changes after binding to the receptor, creating channels in the host cell membrane. The viral genome is then “injected” into the host cell through these channels in a manner analogous to that used by many bacteriophages. Enveloped viruses also have two ways of entering cells after binding to their receptors: receptor-mediated endocytosis and fusion. Many enveloped viruses enter the cell by receptor-mediated endocytosis in a fashion similar to some non-enveloped viruses. On the other hand, fusion only occurs with enveloped virions. These viruses, which include HIV among others, use special fusion proteins in their envelopes to cause the envelope to fuse with the plasma membrane of the cell, thus releasing the genome and capsid of the virus into the cell cytoplasm.
After making their proteins and copying their genomes, animal viruses complete the assembly of new virions and exit the cell. Using the example of HIV, enveloped animal viruses may bud from the cell membrane as they assemble themselves, taking a piece of the cell’s plasma membrane in the process. On the other hand, non-enveloped viral progeny, such as rhinoviruses, accumulate in infected cells until there is a signal for lysis or apoptosis, and all virions are released together.
Animal viruses are associated with a variety of human diseases. Some of them follow the classic pattern of acute disease, where symptoms worsen for a short period followed by the elimination of the virus from the body by the immune system with eventual recovery from the infection. Examples of acute viral diseases are the common cold and influenza. Other viruses cause long-term chronic infections, such as the virus causing hepatitis C, whereas others, like herpes simplex virus, cause only intermittent symptoms. Still other viruses, such as human herpes viruses 6 and 7, which in some cases can cause the minor childhood disease roseola, often successfully cause productive infections without causing any symptoms at all in the host; these patients have an asymptomatic infection.
In hepatitis C infections, the virus grows and reproduces in liver cells, causing low levels of liver damage. The damage is so low that infected individuals are often unaware that they are infected, with many infections only detected by routine blood work on patients with risk factors such as intravenous drug use. Since many of the symptoms of viral diseases are caused by immune responses, a lack of symptoms is an indication of a weak immune response to the virus. This allows the virus to escape elimination by the immune system and persist in individuals for years, while continuing to produce low levels of progeny virions in what is known as a chronic viral disease. Chronic infection of the liver by this virus leads to a much greater chance of developing liver cancer, sometimes as much as 30 years after the initial infection.
As mentioned, herpes simplex virus can remain in a state of latency in nervous tissue for months, even years. As the virus “hides” in the tissue and makes few if any viral proteins, there is nothing for the immune response to act against; immunity to the virus slowly declines. Under certain conditions, including various types of physical and psychological stress, the latent herpes simplex virus may be reactivated and undergo a lytic replication cycle in the skin, causing the lesions associated with the disease. Once virions are produced in the skin and viral proteins are synthesized, the immune response is again stimulated and resolves the skin lesions in a few days by destroying viruses in the skin. As a result of this type of replicative cycle, appearances of cold sores and genital herpes outbreaks only occur intermittently, even though the viruses remain in the nervous tissue for life. Latent infections are common with other herpes viruses as well, including the varicella-zoster virus that causes chickenpox. After having a chickenpox infection in childhood, the varicella-zoster virus can remain latent for many years and reactivate in adults to cause the painful condition known as “shingles”.
At one time or another, we have all most likely been infected with a virus. The common cold and chicken pox are two common examples of ailments caused by animal viruses. Animal viruses are intracellular obligate parasites, meaning that they rely on the host animal cell completely for reproduction. They use the host's cellular components to replicate, then leave the host cell to infect other cells throughout the organism. Examples of viruses that infect humans include chickenpox, measles, influenza, HIV, and herpes.
Viruses gain entry into host cells via several sites such as the skin, gastrointestinal tract, and respiratory tract. Once an infection has occurred, the virus may replicate in host cells at the site of infection or they may also spread to other locations. Animal viruses typically spread throughout the body mainly by way of the bloodstream, but can also be spread via the nervous system.
- Animal viruses rely purely on the host cell for reproduction so are termed intracellular obligate parasites.
- Viruses use the cellular infrastructure of the host cell to replicate and then leave the host cell to infect other cells in a similar manner.
- Viruses can cause different types of infection that include persistent infection, latent infection and oncogenic viral infections.
- Animal virus types include both double-stranded DNA and single-stranded DNA along with double-stranded RNA and single-stranded RNA types.
- Vaccines are usually preventative and are developed from harmless virus variants. They are designed to stimulate the body to have an immune response against the 'real' virus.
A virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or via glycoproteins embedded in the viral envelope. The specificity of this interaction determines the host—and the cells within the host—that can be infected by a particular virus. This can be illustrated by thinking of several keys and several locks, where each key will fit only one specific lock.
Link to Learning
This video explains how influenza attacks the body.
By the end of this section, you will be able to do the following:
- List the steps of replication and explain what occurs at each step
- Describe the lytic and lysogenic cycles of virus replication
- Explain the transmission of plant and animal viruses
- Discuss some of the diseases caused by plant and animal viruses
- Discuss the economic impact of plant and animal viruses
Viruses are obligate, intracellular parasites. A virus must first recognize and attach to a specific living cell prior to entering it. After penetration, the invading virus must copy its genome and manufacture its own proteins. Finally, the progeny virions must escape the host cell so that they can infect other cells. Viruses can infect only certain species of hosts and only certain cells within that host. Specific host cells that a virus must occupy and use to replicate are called permissive . In most cases, the molecular basis for this specificity is due to a particular surface molecule known as the viral receptor on the host cell surface. A specific viral receptor is required for the virus to attach. In addition, differences in metabolism and host-cell immune responses (based on differential gene expression) are a likely factor in determining which cells a virus may target for replication.
Steps of Virus Infections
A virus must use its host-cell processes to replicate. The viral replication cycle can produce dramatic biochemical and structural changes in the host cell, which may cause cell damage. These changes, called cytopathic effects , can change cell functions or even destroy the cell. Some infected cells, such as those infected by the common cold virus known as rhinovirus, die through lysis (bursting) or apoptosis (programmed cell death or “cell suicide”), releasing all progeny virions at once. The symptoms of viral diseases result both from such cell damage caused by the virus and from the immune response to the virus, which attempts to control and eliminate the virus from the body.
Many animal viruses, such as HIV (human immunodeficiency virus) , leave the infected cells of the immune system by a process known as budding , where virions leave the cell individually. During the budding process, the cell does not undergo lysis and is not immediately killed. However, the damage to the cells that the virus infects may make it impossible for the cells to function normally, even though the cells remain alive for a period of time. Most productive viral infections follow similar steps in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release ((Figure)).
A virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or via glycoproteins embedded in the viral envelope. The specificity of this interaction determines the host—and the cells within the host—that can be infected by a particular virus. This can be illustrated by thinking of several keys and several locks, where each key will fit only one specific lock.
This video explains how influenza attacks the body.
Viruses may enter a host cell either with or without the viral capsid. The nucleic acid of bacteriophages enters the host cell “naked,” leaving the capsid outside the cell. Plant and animal viruses can enter through endocytosis (as you may recall, the cell membrane surrounds and engulfs the entire virus). Some enveloped viruses enter the cell when the viral envelope fuses directly with the cell membrane. Once inside the cell, the viral capsid degrades, and then the viral nucleic acid is released and becomes available for replication and transcription.
Replication and Assembly
The replication mechanism depends on the viral genome. DNA viruses usually use host-cell proteins and enzymes to replicate the viral DNA and to transcribe viral mRNA, which is then used to direct viral protein synthesis. RNA viruses usually use the RNA core as a template for synthesis of viral genomic RNA and mRNA. The viral mRNA directs the host cell to synthesize viral enzymes and capsid proteins, and assemble new virions.
Of course, there are exceptions to this pattern. If a host cell does not provide the enzymes necessary for viral replication, viral genes supply the information to direct synthesis of the missing proteins. Retroviruses, such as HIV (group VI of the Baltimore classification scheme), have an RNA genome that must be reverse transcribed into DNA, which then is incorporated into the host cell genome. To convert RNA into DNA, retroviruses must contain genes that encode the virus-specific enzyme reverse transcriptase that transcribes an RNA template to DNA. Reverse transcription never occurs in uninfected host cells—the enzyme reverse transcriptase is only derived from the expression of viral genes within the infected host cells. The fact that HIV produces some of its own enzymes not found in the host has allowed researchers to develop drugs that inhibit these enzymes without affecting the host’s metabolism.
This approach has led to the development of a variety of drugs used to treat HIV and has been effective at reducing the number of infectious virions (copies of viral RNA) in the blood to non-detectable levels in many HIV-infected individuals.
The last stage of viral replication is the release of the new virions produced in the host organism, where they are able to infect adjacent cells and repeat the replication cycle. As you’ve learned, some viruses are released when the host cell dies, and other viruses can leave infected cells by budding through the membrane without directly killing the cell.
Influenza virus is packaged in a viral envelope that fuses with the plasma membrane. This way, the virus can exit the host cell without killing it. What advantage does the virus gain by keeping the host cell alive?
Watch a video on viruses, identifying structures, modes of transmission, replication, and more.
Different Hosts and Their Viruses
As you’ve learned, viruses often infect very specific hosts, as well as specific cells within the host. This feature of a virus makes it specific to one or a few species of life on Earth. On the other hand, so many different types of viruses exist on Earth that nearly every living organism has its own set of viruses trying to infect its cells. Even prokaryotes, the smallest and simplest of cells, may be attacked by specific types of viruses. In the following section, we will look at some of the features of viral infection of prokaryotic cells. As we have learned, viruses that infect bacteria are called bacteriophages ((Figure)). Archaea have their own similar viruses.
Most bacteriophages are dsDNA viruses, which use host enzymes for DNA replication and RNA transcription. Phage particles must bind to specific surface receptors and actively insert the genome into the host cell. (The complex tail structures seen in many bacteriophages are actively involved in getting the viral genome across the prokaryotic cell wall.) When infection of a cell by a bacteriophage results in the production of new virions, the infection is said to be productive . If the virions are released by bursting the cell, the virus replicates by means of a lytic cycle ((Figure)). An example of a lytic bacteriophage is T4, which infects Escherichia coli found in the human intestinal tract. Sometimes, however, a virus can remain within the cell without being released. For example, when a temperate bacteriophage infects a bacterial cell, it replicates by means of a lysogenic cycle ((Figure)), and the viral genome is incorporated into the genome of the host cell. When the phage DNA is incorporated into the host-cell genome, it is called a prophage . An example of a lysogenic bacteriophage is the λ (lambda) virus, which also infects the E. coli bacterium. Viruses that infect plant or animal cells may sometimes undergo infections where they are not producing virions for long periods. An example is the animal herpesviruses, including herpes simplex viruses, the cause of oral and genital herpes in humans. In a process called latency , these viruses can exist in nervous tissue for long periods of time without producing new virions, only to leave latency periodically and cause lesions in the skin where the virus replicates. Even though there are similarities between lysogeny and latency, the term lysogenic cycle is usually reserved to describe bacteriophages. Latency will be described in more detail in the next section.
Which of the following statements is false?
- In the lytic cycle, new phages are produced and released into the environment.
- In the lysogenic cycle, phage DNA is incorporated into the host genome.
- An environmental stressor can cause the phage to initiate the lysogenic cycle.
- Cell lysis only occurs in the lytic cycle.
Most plant viruses, like the tobacco mosaic virus, have single-stranded (+) RNA genomes. However, there are also plant viruses in most other virus categories. Unlike bacteriophages, plant viruses do not have active mechanisms for delivering the viral genome across the protective cell wall. For a plant virus to enter a new host plant, some type of mechanical damage must occur. This damage is often caused by weather, insects, animals, fire, or human activities like farming or landscaping. Movement from cell to cell within a plant can be facilitated by viral modification of plasmodesmata (cytoplasmic threads that pass from one plant cell to the next). Additionally, plant offspring may inherit viral diseases from parent plants. Plant viruses can be transmitted by a variety of vectors, through contact with an infected plant’s sap, by living organisms such as insects and nematodes, and through pollen. The transfer of a virus from one plant to another is known as horizontal transmission , whereas the inheritance of a virus from a parent is called vertical transmission .
Symptoms of viral diseases vary according to the virus and its host ((Figure)). One common symptom is hyperplasia , the abnormal proliferation of cells that causes the appearance of plant tumors known as galls . Other viruses induce hypoplasia , or decreased cell growth, in the leaves of plants, causing thin, yellow areas to appear. Still other viruses affect the plant by directly killing plant cells, a process known as cell necrosis . Other symptoms of plant viruses include malformed leaves black streaks on the stems of the plants altered growth of stems, leaves, or fruits and ring spots, which are circular or linear areas of discoloration found in a leaf.
|Some Common Symptoms of Plant Viral Diseases|
|Hypoplasia||Thinned, yellow splotches on leaves|
|Cell necrosis||Dead, blackened stems, leaves, or fruit|
|Abnormal growth patterns||Malformed stems, leaves, or fruit|
|Discoloration||Yellow, red, or black lines, or rings in stems, leaves, or fruit|
Plant viruses can seriously disrupt crop growth and development, significantly affecting our food supply. They are responsible for poor crop quality and quantity globally, and can bring about huge economic losses annually. Others viruses may damage plants used in landscaping. Some viruses that infect agricultural food plants include the name of the plant they infect, such as tomato spotted wilt virus, bean common mosaic virus, and cucumber mosaic virus. In plants used for landscaping, two of the most common viruses are peony ring spot and rose mosaic virus. There are far too many plant viruses to discuss each in detail, but symptoms of bean common mosaic virus result in lowered bean production and stunted, unproductive plants. In the ornamental rose, the rose mosaic disease causes wavy yellow lines and colored splotches on the leaves of the plant.
Animal viruses, unlike the viruses of plants and bacteria, do not have to penetrate a cell wall to gain access to the host cell. The virus may even induce the host cell to cooperate in the infection process. Non-enveloped or “naked” animal viruses may enter cells in two different ways. As a protein in the viral capsid binds to its receptor on the host cell, the virus may be taken inside the cell via a vesicle during the normal cell process of receptor-mediated endocytosis. An alternative method of cell penetration used by non-enveloped viruses is for capsid proteins to undergo shape changes after binding to the receptor, creating channels in the host cell membrane. The viral genome is then “injected” into the host cell through these channels in a manner analogous to that used by many bacteriophages.
Enveloped viruses also have two ways of entering cells after binding to their receptors: receptor-mediated endocytosis, or fusion . Many enveloped viruses enter the cell by receptor-mediated endocytosis in a fashion similar to that seen in some non-enveloped viruses. On the other hand, fusion only occurs with enveloped virions. These viruses, which include HIV among others, use special fusion proteins in their envelopes to cause the envelope to fuse with the plasma membrane of the cell, thus releasing the genome and capsid of the virus into the cell cytoplasm.
After making their proteins and copying their genomes, animal viruses complete the assembly of new virions and exit the cell. As we have already discussed using the example the influenza virus, enveloped animal viruses may bud from the cell membrane as they assemble themselves, taking a piece of the cell’s plasma membrane in the process. On the other hand, non-enveloped viral progeny, such as rhinoviruses, accumulate in infected cells until there is a signal for lysis or apoptosis, and all virions are released together.
As you will learn in the next module, animal viruses are associated with a variety of human diseases. Some of them follow the classic pattern of acute disease , where symptoms get increasingly worse for a short period followed by the elimination of the virus from the body by the immune system and eventual recovery from the infection. Examples of acute viral diseases are the common cold and influenza. Other viruses cause long-term chronic infections , such as the virus causing hepatitis C, whereas others, like herpes simplex virus, only cause intermittent symptoms. Still other viruses, such as human herpesviruses 6 and 7, which in some cases can cause the minor childhood disease roseola, often successfully cause productive infections without causing any symptoms at all in the host, and thus we say these patients have an asymptomatic infection .
In hepatitis C infections, the virus grows and reproduces in liver cells, causing low levels of liver damage. The damage is so low that infected individuals are often unaware that they are infected, and many infections are detected only by routine blood work on patients with risk factors such as intravenous drug use. On the other hand, since many of the symptoms of viral diseases are caused by immune responses, a lack of symptoms is an indication of a weak immune response to the virus. This allows the virus to escape elimination by the immune system and persist in individuals for years, all the while producing low levels of progeny virions in what is known as a chronic viral disease. Chronic infection of the liver by this virus leads to a much greater chance of developing liver cancer, sometimes as much as 30 years after the initial infection.
As already discussed, herpes simplex virus can remain in a state of latency in nervous tissue for months, even years. As the virus “hides” in the tissue and makes few if any viral proteins, there is nothing for the immune response to act against, and immunity to the virus slowly declines. Under certain conditions, including various types of physical and psychological stress, the latent herpes simplex virus may be reactivated and undergo a lytic replication cycle in the skin, causing the lesions associated with the disease. Once virions are produced in the skin and viral proteins are synthesized, the immune response is again stimulated and resolves the skin lesions in a few days or weeks by destroying viruses in the skin. As a result of this type of replicative cycle, appearances of cold sores and genital herpes outbreaks only occur intermittently, even though the viruses remain in the nervous tissue for life. Latent infections are common with other herpesviruses as well, including the varicella-zoster virus that causes chickenpox. After having a chickenpox infection in childhood, the varicella-zoster virus can remain latent for many years and reactivate in adults to cause the painful condition known as “shingles” ((Figure)).
Some animal-infecting viruses, including the hepatitis C virus discussed above, are known as oncogenic viruses : They have the ability to cause cancer. These viruses interfere with the normal regulation of the host cell cycle either by introducing genes that stimulate unregulated cell growth (oncogenes) or by interfering with the expression of genes that inhibit cell growth. Oncogenic viruses can be either DNA or RNA viruses. Cancers known to be associated with viral infections include cervical cancer, caused by human papillomavirus (HPV) ((Figure)), liver cancer caused by hepatitis B virus, T-cell leukemia, and several types of lymphoma.
Visit the interactive animations showing the various stages of the replicative cycles of animal viruses and click on the flash animation links.
Plant viruses may be transmitted either vertically from parent reproductive cells or horizontally through damaged plant tissues. Viruses of plants are responsible for significant economic damage in both crop plants and plants used for ornamentation. Animal viruses enter their hosts through several types of virus-host cell interactions and cause a variety of infections. Viral infections can be either acute, with a brief period of infection terminated by host immune responses, or chronic, in which the infection persists. Persistent infections may cause chronic symptoms (hepatitis C), intermittent symptoms (latent viruses such a herpes simplex virus 1), or even be effectively asymptomatic (human herpesviruses 6 and 7). Oncogenic viruses in animals have the ability to cause cancer by interfering with the regulation of the host cell cycle.
(Figure) Influenza virus is packaged in a viral envelope that fuses with the plasma membrane. This way, the virus can exit the host cell without killing it. What advantage does the virus gain by keeping the host cell alive?
(Figure) The host cell can continue to make new virus particles.
(Figure) Which of the following statements is false?
- In the lytic cycle, new phages are produced and released into the environment.
- In the lysogenic cycle, phage DNA is incorporated into the host genome.
- An environmental stressor can cause the phage to initiate the lysogenic cycle.
- Cell lysis only occurs in the lytic cycle.
Why can’t dogs catch the measles?
The virus can’t attach to dog cells, because dog cells do not express the receptors for the virus and/or there is no cell within the dog that is permissive for viral replication.
One of the first and most important targets for drugs to fight infection with HIV (a retrovirus) is the reverse transcriptase enzyme. Why?
Reverse transcriptase is needed to make more HIV-1 viruses, so targeting the reverse transcriptase enzyme may be a way to inhibit the replication of the virus. Importantly, by targeting reverse transcriptase, we do little harm to the host cell, since host cells do not make reverse transcriptase. Thus, we can specifically attack the virus and not the host cell when we use reverse transcriptase inhibitors.
In this section, you were introduced to different types of viruses and viral diseases. Briefly discuss the most interesting or surprising thing you learned about viruses.
Answer is open and will vary.
Although plant viruses cannot infect humans, what are some of the ways in which they affect humans?
Plant viruses infect crops, causing crop damage and failure, and considerable economic losses.
A bacteriophage with a lytic life cycle develops a mutation that allows it to now also go through the lysogenic cycle. How would this provide an evolutionary advantage over the other bacteriophages that can only spread through lytic cycles?
In a lysogenic cycle, the bacteriophage integrates into the host bacterium’s genome as a prophage, and is passed on to daughter cells every time a bacterium carrying the prophage replicates. This allows the prophage to be dispersed through a wide population without killing any of the host cells. Since the mutated bacteriophage also retains the ability to switch into the lytic cycle, it now has two methods to disseminate through the bacteria population.
3. Cell Culture (Tissue Culture)
There are three types of tissue culture organ culture, explant culture and cell culture.
Organ cultures are mainly done for highly specialized parasites of certain organs e.g. tracheal ring culture is done for isolation of coronavirus.
Explant culture is rarely done.
Cell culture is mostly used for identification and cultivation of viruses.
- Cell culture is the process by which cells are grown under controlled conditions.
- Cells are grown in vitro on glass or a treated plastic surface in a suitable growth medium.
- At first growth medium, usually balanced salt solution containing 13 amino acids, sugar, proteins, salts, calf serum, buffer, antibiotics and phenol red are taken and the host tissue or cell is inoculated.
- On incubation the cell divide and spread out on the glass surface to form a confluent monolayer.
GK Questions and Answers on Types of Viruses (Biology)
Viruses can infect animals, plants, fungi, and bacteria. The virus sometimes can cause a disease that may be fatal. Some virus may also have one effect on one type of organism, but a different effect on another. Viruses cannot replicate without a host so they are classified as parasitic.
1. Which of the following diseases are caused due to a virus?
D. All the above
Explanation: Viral diseases are diseases that are caused due to virus namely AIDS, Ebola, Influenza, SARS (Severe Acute Respiratory Syndrome), Chikungunya, Small Pox, etc.
2. Name the virus that is transmitted through the biting of infected animals, birds, and insects to a human?
A. Rabies Virus
B. Ebola Virus
D. All the above
Explanation: Transmission of the virus through the biting of infected animals, birds, and insects to humans is known as Zoonoses. Examples: Rabies virus. Alphavirus, Flavivirus, Ebola virus, etc.
3. Based on host range, viruses are classified into:
B. Insect virus
C. Stem Virus
D. Both A and B
Explanation: There are four different types of viruses based on the type of host namely Animal viruses, Plant viruses, Bacteriophage and Insect virus.
4. In the host cell, replication of RNA virus took place in.
Explanation: An example of the replication of the virus within the cytoplasm in the host cell is all RNA virus except the influenza virus.
5. Which of the following statement is correct about viruses?
A. Viruses do not contain a ribosome.
B. Viruses can make protein.
C. Viruses can be categorised by their shapes.
D. Both A and C are correct
Explanation: Viruses do not contain ribosomes, so they cannot make proteins. That is why they are dependent on their host. Viruses have different shapes, sizes and can be categorised by their shapes.
6. Name the virus that covers himself with a modified section of the cell membrane and create a protective lipid envelope?
A. Influenza virus
C. Neither A nor B
D. Both A and B
Explanation: Some viruses cover themselves with a modified section of the cell membrane by creating a protective lipid envelope example the influenza virus and HIV.
7. A virus can spread through:
A. Contaminated food or water
D. All the above
Explanation: Viruses can spread through touch, exchanges of saliva, coughing or sneezing, contaminated food or water and also through insects that carry them from one person to another.
8. After which period virus replicates in the body and starts to affect the host?
A. Incubation period
D. None of the above
Explanation: Virus replicates in the body and starts to affect the host after a period known as the incubation period and symptoms may start to show.
9. Double-stranded DNA is found in which viruses?
C. Influenza viruses
D. None of the above
Explanation: Double-stranded DNA is found in poxviruses, the bacteriophages T2, T4, T6, T3, T7, Lamda, herpes viruses, adenoviruses, etc.
10. A virus is made up of a DNA or RNA genome inside a protein shell known as:
Explanation: A virus that is made up of a DNA or RNA genome inside a protein shell is known as a capsid. Some viruses have an external membrane envelope.
These are a few questions related to viruses, types, structure, classification, etc.
Part 2: Virus Adaptation to Environmental Change
00:00:15.24 I'm Paul Turner from the Department of Ecology and Evolutionary Biology at Yale University,
00:00:19.20 and the Microbiology faculty at Yale School of Medicine.
00:00:23.06 Today, I'd like to present on virus adaptation (or not) to environmental change.
00:00:29.08 This talk describes how viruses have an amazing capacity to adapt to environmental challenges
00:00:35.03 and, yet, we'll find that these champions of adaptation sometimes encounter environments
00:00:40.17 that demonstrate that environmental change can constrain evolution and adaptation, and
00:00:46.13 even these so called champions can face constraint.
00:00:50.11 So, very many challenges exist to viruses in the natural world and you could think of
00:00:56.09 this at all different levels of biological organization.
00:00:59.24 So, if you start at the base level of molecules and cells, the primary challenge for viruses
00:01:06.02 is that they cannot control where they exist in the environment, so they might encounter
00:01:11.04 some cell type and successfully enter if they have the right protein binding to recognize
00:01:16.19 a protein on the cell surface, or they might bump into the wrong type of cell and that
00:01:22.15 protein recognition doesn't occur.
00:01:24.14 So, therefore, it's an immediate and proximate challenge to a virus to infect a cell, depending
00:01:30.02 on where it is in the environment and whether the proper cells exist to infect.
00:01:34.13 In macroorganisms like us, we have tissues composed of different cell types, so if a
00:01:41.00 virus is in your body and it's replicating in one tissue type, it might be challenged
00:01:46.01 to infect a different tissue that's nearby and it's incapable of doing so.
00:01:51.05 Hosts, such as humans, have elaborate and beautiful immune systems.
00:01:56.21 Some of them are adaptive, meaning that they change through time and this is a way of our
00:02:01.08 immune system, in a way, keeping pace with microbial invaders and changing at the same
00:02:07.03 pace that they might evolve through evolution.
00:02:10.00 But viruses and other microbes. when they encounter these immune systems, this poses
00:02:14.23 a challenge for them to continue to infect that host, or that host's progeny, or other
00:02:19.19 susceptible hosts in their env. in their environment, depending on whether those immune
00:02:24.00 systems provide an immediate and successful barrier to virus replication.
00:02:30.10 It's amazing thing that some viruses infect humans and also successfully infect very different
00:02:37.12 organisms that are not at all closely related to us.
00:02:41.11 A great example of this are the arthropods, where many pathogens are vector-transmitted
00:02:47.11 by arthropods such as mosquitoes, including viruses.
00:02:51.14 And this is pretty fascinating, because a virus has to grow within an invertebrate and,
00:02:58.05 for example, in a mosquito, it has to grow in the midgut and eventually get to the salivary
00:03:01.21 glands in order to be present in a bite that puts the virus in the bloodstream of another
00:03:07.04 host to be picked up by another mosquito.
00:03:09.21 That's got to be an incredible challenge for a virus to grow both successfully in an invertebrate,
00:03:14.23 like an arthropod, as well as a vertebrate like you, a human.
00:03:18.18 And, last, we have to remember that global-level ecosystem changes affect all biological entities
00:03:25.04 on this planet, including the very smallest ones such as viruses.
00:03:29.02 So, when you think about challenges like climate change and global warming, you have to remember
00:03:35.11 that this is something that is felt by all biological entities, and therefore viruses
00:03:40.06 can also feel the challenge of an ever-warming world.
00:03:43.23 There are many different virus study systems that my group examines.
00:03:48.11 So, these examples are shown in the very many beautiful forms behind me.
00:03:54.09 On the far left, we have vesicular stomatitis virus, which is an example of a single-stranded
00:03:59.15 RNA virus with a negative-sense genome, and in the middle we have a variety of other viruses,
00:04:04.23 also, that will infect eukaryotes, but they happen to have positive single-stranded RNA
00:04:11.05 Closer to where I'm standing, we have single-stranded DNA filamentous phage, and also double-stranded
00:04:16.17 RNA and double-stranded DNA viruses, in this case, both phages: phage phi-6 and phage T2.
00:04:23.09 So, these are examples within my laboratory of the wide variety of viruses that exist
00:04:28.14 in the natural world, and how a single laboratory can choose to examine this great variety of
00:04:34.11 virus types.
00:04:35.16 Depending on the challenge and the question, we would like to focus on a different study
00:04:39.17 system to examine whether viruses can successfully, or not, adapt to their environments.
00:04:45.21 A big tool that we use that's very popular with others, and a very powerful tool, would
00:04:50.22 be experimental evolution.
00:04:52.24 A way to summarize this method is it's the ability to study evolution in action.
00:04:58.01 So, if you have the right study system in a controlled place, like a laboratory, you
00:05:03.17 can take that population, put it in an environment that you control explicitly, and then examine,
00:05:09.09 how does that population deal with that challenge, both in terms of the traits that it evolves
00:05:14.07 as well as the genotypic changes that it undergoes?
00:05:16.24 So, both phenotype and genotype can be the focus of these studies.
00:05:21.09 An important thing to remember is, even if a researcher is manipulating the environment
00:05:25.20 in the laboratory, it still can be a challenge to a population, and that population can evolve
00:05:32.07 through natural selection.
00:05:33.12 So, you're talking about an artificial environment and yet natural selection can occur.
00:05:38.22 That's because the researcher is not determining which variants in that population will better
00:05:43.17 match the environment instead, that's due entirely to the mutations and the genetics
00:05:48.15 of that system to meet that challenge or not.
00:05:52.18 And that can happen through the process of evolution by natural selection.
00:05:57.11 A typical design is shown here, where we would begin with some ancestral type.
00:06:03.00 We might be interested, in the case of this hypothetical diagram, in three different treatments
00:06:07.12 that differ in some way in their environmental challenge, and we can track, over the course
00:06:13.16 of generations, how do these independent lineages evolve to meet these challenges?
00:06:20.05 And the nice thing is to include replication in these experiments, such as you can have
00:06:24.22 lineages that are experiencing the same environment, and you can look at how consistently do lineages
00:06:30.23 undergo random mutation, and yet the same mutations might be the ones that rise to fixation,
00:06:36.12 and lead to adaptation.
00:06:38.05 In other cases, there might be different solutions to the environmental challenge, and you'll
00:06:42.20 see divergence between your lineages in the sense that different mutations are meeting
00:06:47.20 the same challenge.
00:06:50.10 Another way to think about these experimental evolution studies is to create a hypothetical
00:06:55.09 diagram of some phenotypic trait that you would want measure -- this might be growth
00:07:00.06 or some other capacity of the system to meet the challenge.
00:07:03.03 So, in this example, I'm illustrating how this trait has some variation at the beginning,
00:07:09.21 and then we could create some sort of an ecological circumstance, or an environmental challenge,
00:07:14.22 in these studies, and, through time, we can keep track of how phenotypes change.
00:07:19.18 So, you'll notice that the average phenotype, along the x axis in this hypothetical example,
00:07:25.18 is shifting to the right, meaning that the mean of the distribution is changing according
00:07:29.23 to which variants are in that population and the ones that are best meeting that challenge.
00:07:34.15 Now, we can go further than a lot of systems, because it's very easy for us in virus studies
00:07:40.04 to take the entire genome from these evolving populations and explicitly look everywhere
00:07:46.08 in the genome for where a mutation might occur.
00:07:48.24 In this case, we can track through generational time, how is the genetics changing in relation
00:07:54.11 to the ecological challenge as well?
00:07:56.15 And this allows a lot of immediate power in making something called a phenotype-genotype
00:08:01.14 association -- you can infer how the changing phenotype is being controlled by underlying
00:08:10.10 genetics, and make some base inferences about what the relationship is.
00:08:15.15 And I don't want to trivialize that because one has to do a lot more work to convince
00:08:19.14 oneself that, perhaps, one mutation is responsible, maybe two or three, or even more complex things
00:08:26.00 can occur like these mutations acting with one another through properties like epistasis.
00:08:31.06 So, this provides an amazing amount of power to examine how evolution occurs according
00:08:37.13 to the environment that you create in these types of studies.
00:08:41.12 The outline for what I want to talk about today is pretty much centered on these two
00:08:47.14 We can consider environmental changes as fostering versus constraining virus adaptation, depending
00:08:54.12 on how the environment is constructed, and these types of experiments are in the natural
00:08:59.18 And, especially, now, that takes us to this next question of, are there particular traits
00:09:04.15 that can evolve in viruses that match something intriguing that you see in cellular systems?
00:09:11.06 The investment in survival versus reproduction is often something that's seen as at odds
00:09:16.01 to one another in cellular systems, that you can either invest a lot in survival as an
00:09:21.07 evolutionary trait, but this minimizes your reproductive capacity, or vice versa.
00:09:27.06 So, an intriguing set of studies show that this same constraint, or the same trade-off,
00:09:34.08 can happen even in non-metabolizing organisms, such as the viruses, especially in the viruses.
00:09:42.22 How does environmental change foster versus constrain virus adaptation?
00:09:47.12 Let's look at this question first.
00:09:50.21 Virus emergence is an amazing bio. biomedical challenge that we face today.
00:09:56.01 So, even though RNA viruses, especially, are not that prevalent among the highly prevalent
00:10:01.18 viruses that exist on this planet, they seem to be especially able to jump into new host
00:10:07.20 species and cause harm through disease.
00:10:10.10 So, humans see this through recently emerging pathogens, such as Zika virus, which is sweeping
00:10:17.04 around the globe, and is problematic and creating a challenge to biomedicine, to protect people
00:10:22.16 against Zika virus infection that can disrupt normal development at an early age.
00:10:27.22 A very different example, but still called emergence, is when a virus comes from another
00:10:33.06 species, enters into the human population, and gets locked in and becomes very specific
00:10:39.16 to humans.
00:10:40.16 So, I began with the case of Zika virus, which is not specific to humans, but a great example
00:10:45.17 of a specificity evolution would be HIV, which came into the human population several times,
00:10:51.18 independently, from our primate relatives, especially chimpanzees and certain species
00:10:56.09 of monkeys, and this has led to the evolution of HIV-1 and HIV-2, independently, several
00:11:04.06 A third example of emergence would be something that exists both within humans, as well as
00:11:09.21 in other species, and a great example of that would be influenza virus.
00:11:14.09 So, ordinarily, in any year, you can have plenty of the human population seeing flu
00:11:19.03 virus infection and suffering influenza, but what we fear is that there are certain forms,
00:11:24.12 or genotypes, of influenza virus that will be especially virulent and cause a high degree
00:11:29.05 of mortality, and sweep around the globe to infect a lot of humans, and adversely affect
00:11:34.06 human populations, more than a standard flu season.
00:11:37.03 And, especially, we fear that the large reservoir of influenza viruses, that mostly exist in
00:11:43.05 this planet in waterfowl, might lead to a variant that can jump immediately into humans
00:11:48.16 and then be passed from human to human.
00:11:50.23 This would be an example of a flu virus coming from a bird, coming into a very different
00:11:56.00 host species, a mammal, and causing a lot of destruction and mortality because of the
00:12:00.18 inability of the human immune system to deal with the challenge.
00:12:03.20 So, these are three different examples of the same catalogued thing that thing is what's
00:12:09.20 called emergence, and this is a huge biomedical challenge.
00:12:14.03 We can think of how emergence can or cannot occur for a virus, and that's what I want
00:12:18.09 to focus on next.
00:12:19.11 And there are some certain fundamental expectations, if you have any lineage, whether it's a virus
00:12:25.03 or not, and whether it's encountering an environment that is constant through time, versus changing
00:12:30.21 seasonally, or in a temporal way through time.
00:12:34.22 So, I'm giving two hypothetical examples of this.
00:12:38.11 At the top, we have a hypothetical evolving lineage that sees niche A and niche B in a
00:12:44.22 flip-flopping fashion, and each one of these little circles indicates a generation.
00:12:49.23 So, necessarily, this lineage has to grow in environment A in order to make it long
00:12:55.04 enough in its environment to reach a new environment, B, and so on.
00:12:59.18 Necessarily, we would expect that this. this will select for generalization -- the
00:13:03.18 ability to thrive in both of these environments -- because there is no other option.
00:13:08.06 Now, that's very different than if that lineage has the luxury of seeing only a single environment.
00:13:13.11 In this case, environment A is the only thing it encounters, but I'm underlining the word
00:13:19.18 *tends* to select for specialization, because that's only one possibility.
00:13:24.07 This luxury affords this possibility of being highly specific to your environment and being
00:13:28.23 very good in that environment, but it also is an opportunity for generalization to occur,
00:13:35.15 if you have a correlated response to growing well in other environments.
00:13:39.04 And, essentially, that must be happening in emerging virus pathogens.
00:13:43.16 They happen to have the right genetic capacity that when they jump into a new host species
00:13:48.04 like human, they can just really hit the ground running and grow very well, cause a lot of
00:13:53.15 damage, and ultimately they might be specific to that environment. ultimately, but initially
00:13:59.17 they're highly generalized.
00:14:02.12 We've covered this topic in a variety of papers that I'm listing here that I won't have time
00:14:06.05 to go into much detail, but one can think of this challenge of virus specialism versus
00:14:11.22 generalism happening a lot in the natural world, and it's very easy and powerful to
00:14:17.05 study this in the laboratory, through the experimental evolution method that I mentioned
00:14:23.14 One system that we've focused on a lot to study how virus specialization versus generalization,
00:14:29.01 and just simply adaptation can happen, is a model known as vesicular stomatitis virus.
00:14:34.17 So, this is a single-stranded RNA virus with a negative-sense genome that's pretty much
00:14:39.21 a workhorse in molecular virology.
00:14:42.06 It's been used for very many decades to understand fundamentals of how RNA viruses infect and
00:14:47.17 replicate in a cell.
00:14:49.05 So, some pictures, here, that I'm showing are just to reflect that we have a lot of
00:14:53.16 prior knowledge for the molecular details of this system, and that's great when you
00:14:58.14 enter into experimental evolution studies, because you don't have to go about measuring
00:15:03.06 that stuff all over again you can think of the outcome of your experiments in the context
00:15:07.17 of the prior knowledge.
00:15:08.19 So, VSV has a very small genome in size.
00:15:11.21 It has only 11 kilobases in length.
00:15:15.08 And this comprises only 5 genes.
00:15:17.04 So, one can think of this as a pretty simple system.
00:15:20.04 And yet it has a pretty amazing capacity to do things like both reproduce in an arthropod
00:15:26.15 -- it's an arthropod-borne virus or an arbovirus -- and it also can replicate in a mammal.
00:15:31.13 So, in the case of VSV, it's a safe system to use in the laboratory because it might
00:15:36.08 get in a human by accident, but it really doesn't cause much harm.
00:15:40.07 It's agriculturally important in large mammals, domesticated horses, etc, so we do care about
00:15:45.14 it from a disease standpoint, but it's a great, powerful system to use in the laboratory,
00:15:52.04 It comes from the family rhabdoviridae, which also features rabies virus.
00:15:58.04 Here's a summary of some of the data from one of our experiments, where we harnessed
00:16:03.06 experimental evolution to examine, how does this virus deal with a constant environment
00:16:09.11 versus one that is changing through time in that temporal heterogeneous way that I outlined?
00:16:14.10 So, this is a pretty busy diagram, but I'll walk you through it.
00:16:18.02 At the top, this is merely a depiction of the VSV genome and the 5 genes N, P, M, G,
00:16:24.14 L. And what you can see is, for each one of the lineages ,the 4 lineages that saw only,
00:16:30.10 in this case, HeLa cells. those are cancer-derived cells that originally came from Henrietta
00:16:35.22 Lacks a long time ago, and these were harnessed as an immortalized cell line that people use
00:16:41.08 and a lot of studies beyond simply virus studies. but these cancer-derived cells provided a
00:16:47.07 new challenge for VSV in this experiment, and each one of the points, here, on the diagram,
00:16:52.19 are showing where these lineages changed in their genetic material relative to the ancestor
00:16:59.12 after the experiment took place.
00:17:01.18 In this way, we can catalogue, what are the mutations that arose, and which ones fixed
00:17:06.10 through natural selection, to let these lineages improve in their environment?
00:17:12.00 We also did an exp. in this experiment a challenge where the viruses had to not only
00:17:15.23 evolve on HeLa cells, but, in an alternating fashion, they had to enter into a non-cancer-derived
00:17:22.12 cell type, abbreviated as MDCK, and in this way they had to become adapted to both HeLa
00:17:28.12 cells as well as these non-cancer cells.
00:17:31.18 And you'll see that we also catalogued their genetic changes through time.
00:17:35.24 And this has a great deal of variety, even within each treatment, for the mutations that
00:17:41.15 fixed according to each lineage.
00:17:44.02 One can also catalogue the exact position where each one of these mutations took place.
00:17:48.12 Let me highlight one more thing before I move on, and that is, really, these virus populations,
00:17:55.08 after this experiment, are not carbon copies of one another.
00:17:58.19 So, there are many places where we do see that they underwent the same mutational change
00:18:04.08 at exactly the same place, and that must be evidence of some beneficial mutation coming
00:18:10.01 in and fixing in these lineages.
00:18:12.15 And yet, in some genes, they underwent different mutations from even the same populations in
00:18:17.21 the same treatment, so this indicates that there can be other genetic solutions to the
00:18:22.22 same environmental problem in a study like this.
00:18:26.06 Keep this in mind as we go on and look at a subsequent experiment that challenged the
00:18:31.02 ability of these viruses to evolve and infect yet new hosts to test, what is their emergence
00:18:39.01 Simply remember that we lumped them together as specialists, having seen only one constant
00:18:44.05 host hype, or generalists, that were selected to see two types, and yet the lineages are
00:18:49.10 not carbon copies of one another when they're drawn from each treatment.
00:18:53.16 Here, we wanted to ask a very fundamental question that's really at the root of what
00:18:58.15 lets emergence occur.
00:19:00.11 So, a popular idea is that, if some pathogen has seen multiple hosts in the past, it's
00:19:07.02 somehow groomed through adaptation to be generalized enough that it will successfully enter and
00:19:13.16 infect a new host when it sees it just randomly through encountering it in nature.
00:19:19.08 That's because adaptation has primed that pathogen to be good at growing in multiple
00:19:23.24 hosts and, through correlated response, it just might grow very well in a new host such
00:19:28.13 as humans.
00:19:29.13 So, here, I'm depicting a picture of Henrietta Lacks, as the. ultimately, the person who
00:19:34.16 gave rise to these HeLa cells that we used in this experiment, and we asked, whether
00:19:39.13 viruses that evolved strictly on HeLa cells, are they going to be good at growing on a
00:19:45.06 variety of challenge hosts that we purchased?
00:19:48.20 Or are we going to fit with this prediction that selected generalists were pre-adapted
00:19:55.06 in some way to perform well on these new hosts and they should be the ones that we would
00:20:00.00 fear as typical of a successful emerging pathogen, something that's groomed to grow on multiple
00:20:06.01 hosts and will grow well on a challenge host when it encounters it?
00:20:10.24 To go to the data from an earlier paper, this is pretty well supported by our study, that,
00:20:17.15 yes, selected generalists emerge or they shift hosts easier.
00:20:21.16 So, this diagram is showing, what is the sheer reproductive capacity of each of these virus
00:20:28.04 lineages, indicated by each point, relative to its ability to grow in the environment
00:20:33.19 that it was previously evolved on?
00:20:35.22 So, this gives an indication of. relative to its ordinary reproductive capacity, is
00:20:41.16 it any better or equally good at growing on a new challenge host, relative to the host
00:20:46.18 that it saw prior to adaptation?
00:20:49.13 And you'll see that all the blue points are well below the zero line.
00:20:53.19 That means that these specialist viruses from our study, they can grow on this first challenge
00:20:59.16 host I'm indicating, that came from monkey cells, but they grow pretty poorly compared
00:21:04.02 to their capacity to grow on the HeLa cells that came from Henrietta Lacks, whereas the
00:21:09.06 selected generalists, they saw both host types in our prior experiment -- one happened to
00:21:15.05 be cancer-derived, one happened to be non-cancer-derived -- but those were different enough cell types
00:21:20.09 that have provided a challenge to adapt to two things simultaneously.
00:21:25.03 And you'll see that, on this challenge host, those selected generalists actually did a
00:21:29.07 better job at growing on a challenge host that was just randomly chosen and presented
00:21:34.05 to them.
00:21:35.16 All four of those triangles are very close to the zero line.
00:21:38.22 So, in summary, one could say that, in this first line of evidence, on the monkey cells,
00:21:45.00 there's both a higher mean, on average, and lesser variance across the populations drawn
00:21:50.15 from each treatment for the selected generalist to do better.
00:21:53.24 Now, if you look at all four challenge hosts, there's an amazing ability for the data to
00:22:00.21 look highly similar, no matter what the challenge host was that we randomly entered into this
00:22:05.18 experiment using.
00:22:07.02 And, to me, that's fascinating, because it indicates that there's hardly any of what
00:22:11.22 one would call genotype-by-environment interaction.
00:22:14.22 This must be due to the capacity of these viruses to just simply grow on something new,
00:22:20.17 and it's not really the interaction with that new thing, it's just that they can grow better
00:22:25.02 on something that they've been challenged to infect.
00:22:27.07 So, this provides nice evidence in four randomly chosen challenges that selected generalists
00:22:33.21 can grow much better on a new host that you present them with, and this gives us a little
00:22:38.13 more insight at what could be the root of the emergence problem.
00:22:42.16 But I haven't really told you why -- why is this happening?
00:22:48.10 Why is it that these selected generalists actually emerge easier at a mechanistic level?
00:22:53.20 Here, we've looked at the ability, the innate immune ability, of cell types, and whether
00:22:59.24 selected generalists were keying in on this line of immunity and navigating their way
00:23:05.24 through it, and if they have a generalized ability to do that, and that should carry
00:23:10.22 over to other challenge types, even though that challenge type would be drawn from a
00:23:15.08 different species.
00:23:16.16 So, this is a very detailed diagram, but it's showing some of the inner workings at the
00:23:21.11 cellular level of something that you're born with.
00:23:24.22 This is the innate immune capacity of your cells that, when they see an invader, like
00:23:29.22 a virus, that they will be able to undergo a cascade of events at the cellular level
00:23:35.13 that gives them protection against that virus infection.
00:23:39.00 And, interestingly, the signals can go out to cells that are nearby in the tissue neighborhood
00:23:45.14 to prime them to be better protected against that virus, before the virus even is able
00:23:51.08 to replicate enough to get to those cell types.
00:23:53.24 Now, this is a wonderful ability, to be immune to a pathogen, that you should remember this
00:24:00.00 is your innate immunity.
00:24:02.13 Adaptive immunity, which people are much more familiar with, is something that is occurring
00:24:06.08 much longer-term, and it takes weeks or even longer that you see a pathogen and you mount
00:24:11.00 an immune response to the its uniqueness.
00:24:13.07 Here, this is just a generalized thing that controls pathogen infections.
00:24:18.06 So, before I move on, I'll say that the VSV M protein, or the matrix protein, is known
00:24:25.09 to be the thing that interacts with the capacity of a cell to produce its anti-immune response
00:24:31.11 to virus infection, especially interferon.
00:24:34.06 So, ordinarily, this cell is going to be producing interferon as one of these key chemicals that
00:24:39.09 protects it, and signals go out and interferon production occurs in other cells in the tissue
00:24:44.18 to protect them, but VSV, as a virus, can infect a cell and down-regulate that response.
00:24:53.05 And that helps us even explain how we even did the prior experiment.
00:24:56.19 VSV has a great capacity, just as a virus, to grow in a variety of cell types, because
00:25:03.18 it can regulate this response.
00:25:06.08 However, it could be that viruses like VSV are highly generalized in moving between hosts
00:25:14.18 because they properly regulate that immunity cascade.
00:25:19.15 So, without very many details, this is a hypothetical idea of how this can occur, and what one should
00:25:26.24 So, let's imagine that the prior selection history of some virus or other pathogen, this
00:25:32.19 is relating its fitness, due to that prior evolution, in terms of whether it saw host
00:25:38.22 types that are of low or high innate immunity.
00:25:41.23 So, in our prior experiment, I highlighted in blue how these specialist viruses perform
00:25:48.12 very well on HeLa cells, but I didn't tell you one key bit of information about a lot
00:25:54.15 of cancer cells, including HeLa cells.
00:25:57.03 They have very low or completely absent innate immunity.
00:26:01.00 So, what happened in that experiment, probably, is that the lineages of viruses evolved to
00:26:06.03 infect a cell type where they didn't really have to worry at all about innate immunity
00:26:10.17 as a challenge in infecting and growing in the cell type.
00:26:14.00 So, this probably led to de-evolution, or the removal of the capacity for those viruses
00:26:20.09 to control innate immunity.
00:26:22.00 They just simply didn't need it.
00:26:24.05 And then, when you challenged them to grow on a new host type, they are very handicapped
00:26:28.19 in doing so because they don't have the capacity to track the innate immunity functions within
00:26:33.08 a cell.
00:26:34.09 Whereas, viruses could see, necessarily, in our experiment, both high and low innate immunity,
00:26:40.24 because we used cancer-derived as well as non-cancer-derived cells, so they remained
00:26:45.13 capable of navigating through both cell types, and when they see a new cell type they can
00:26:50.15 hit the ground running.
00:26:52.06 So, importantly, one can think of both alternating hosts as, necessarily, in our experiment,
00:26:59.17 keeping this capacity, but it also could have been, and we've done work like this. if
00:27:04.08 you take virus lineages and you grow them only on high innate immunity hosts, you get
00:27:09.16 a very similar capacity for them to maintain strong growth regardless of cell type.
00:27:15.15 So, we have both good news and bad news in predicting emergence.
00:27:19.21 We have the ability for selected generalists to key in on innate cell function and navigate
00:27:25.09 multiple cell types, and you'd expect them to emerge, but they don't have to do that.
00:27:30.03 They could still successfully emerge through a correlated response.
00:27:34.00 So, the next question I want to cover is whether the environmental change that is presented
00:27:40.17 to viruses either fosters or constrains their adaptation.
00:27:44.05 So, now, this is a similar diagram that I showed you before, but note that now I'm including
00:27:48.17 a different kind of a challenge.
00:27:50.19 Here's where the lineage sees pretty much a stochastic set of environments through time.
00:27:56.03 In other words, it's moving from environment to environment, but there doesn't seem to
00:28:00.13 be any pattern to what that. what those environments present, right?
00:28:04.10 So, these are shown as separate colors in this diagram to illustrate how some virus
00:28:09.10 lineages might have to navigate through very different environments, and one can create
00:28:14.02 an experiment that says, well, will these champions of adaptations still be able to
00:28:19.12 successfully navigate through such a complex set of environments and become generalized?
00:28:24.20 Or is this just simply too much and, even in champions of adaptation like RNA viruses,
00:28:30.08 they'll be constrained and unable to do this?
00:28:34.04 This actually relates in some way to certain models that come from climate change, where
00:28:40.02 the prediction is. really, the fundamental problem for evolving lineages in climate change
00:28:46.05 is that stochasticity of the environment becomes more important.
00:28:50.07 The environment simply becomes more variable through time and it will be harder for lineages
00:28:54.21 to track those changes.
00:28:56.23 Well, it should be interesting to see whether viruses can successfully do this, because,
00:29:02.10 if they cannot, then this bodes pretty bad news for other organisms that have a much
00:29:07.12 slower and reduced capacity to evolve in the face of environmental challenges.
00:29:12.11 So, let's see what happened.
00:29:14.20 one can easily construct an experiment like this, but, rather than creating host challenges
00:29:20.04 through time, let's think a little bit more about those climate change models and the
00:29:24.01 thing that we'll manipulate is temperature through time.
00:29:26.14 So, in this diagram I'm showing four different treatment groups that were created in an experiment,
00:29:31.24 where 37 degrees Celsius is the upper limit, or pretty much the ordinary temperature for
00:29:37.01 replication that we use in the laboratory for VSV 29 degrees Celsius is a lower temperature,
00:29:44.00 where they can still grow but it's much lower than 37 C, 8 degrees lower and then we have
00:29:49.17 alternating lineages that will see these two environments in a flip-flopping fashion and
00:29:55.12 then we include this fourth treatment, this is really the intriguing one.
00:29:58.21 If you take that 8-degree window and you go into the laboratory and you challenge the
00:30:03.06 viruses to grow at any temperature in the 8-degree window that you randomly choose on
00:30:07.10 that day, it will create a very stochastic environment through time.
00:30:12.00 And here we want to know, across generations, especially 100 generations, is there any differing
00:30:17.09 capacity of these viruses to evolve well in the face of this challenge?
00:30:22.06 So, we can go immediately to the data that came from this experiment.
00:30:26.04 And the way this graph works is it shows you, what is the fitness after 100 generations
00:30:30.24 for each one of these lineages, at each edge of the niche space?
00:30:35.02 So, it's plotted, what is their fitness at 37 C versus their fitness at 29 C?
00:30:40.24 And the intersection of those points leads to each point on the graph.
00:30:44.11 So, you'll see that the lineages that evolved in a constant high-temperature environment
00:30:49.00 improved in that environment -- in other words, all their data are to the right and above
00:30:55.05 the dashed lines on this figure.
00:30:57.03 They've improved both in terms of the environmental challenge they saw -- 37 C -- as well as 29
00:31:03.21 C, which was the other environment that was constant in this experiment.
00:31:07.02 That's evidence of correlated selection -- you improve in one environment and it also allows
00:31:12.05 you to improve in another environment that you haven't seen.
00:31:15.01 The same thing occurred for the lineages that saw only 29 C as the challenge.
00:31:20.08 Interestingly, in green, we have an alternating environment, where populations improved, in
00:31:27.09 some cases more than populations that saw only a constant environment.
00:31:32.10 And that's intriguing because it shows that populations can improve even though they see
00:31:36.11 the challenge only half the time as their counterparts.
00:31:40.08 It must be that the genetics that underlies this, which we've shown in papers that I won't
00:31:44.00 present today, is that different mutations are responsible for this improvement in an
00:31:48.09 alternating environment versus a constant one, but, in both cases, you can have improvement
00:31:53.03 relative to the ancestor.
00:31:55.08 Most intriguing in this data set is shown in purple, where all of those purple points
00:31:59.23 and lines are nestled right near the intersection of the dashed lines, which show the ancestral
00:32:06.10 This means that the random treatment in the pop. in the experimental evolution study.
00:32:12.09 these lineages did not improve any more than the ancestral performance.
00:32:17.13 In other words, the stochasticity of the environment was too much for them to deal with, and that's
00:32:22.11 bad news in terms of these champions of adaptation.
00:32:26.08 If they can't handle stochastic environments, then that bodes ill for more complex organisms
00:32:32.20 that have much slower adaptive and evolutionary capacity -- we wouldn't expect them to thrive
00:32:38.07 either, or to improve in fitness, when seeing stochastic change.
00:32:43.16 This is pointed to in the diagram in terms of the intersection of the points, and all
00:32:47.20 those purple points nestled near the dashed lines and their intercept, as indicative of
00:32:53.22 adaptive constraint.
00:32:56.20 The next question will be, do viruses evolve survival reproduction trade-offs that we observe
00:33:01.16 in cellular life?
00:33:03.00 Here, we want to examine whether the capacity to adapt in one means, and that is to produce
00:33:09.13 progeny, is something that detracts from the capacity to merely survive in the environment
00:33:15.02 when it poses a challenge.
00:33:16.02 We've seen in cellular systems that you can't have your cake and eat it too, in terms of
00:33:22.02 these two challenges improving through time, that you can either invest in survival or
00:33:26.21 reproduction, but often you have an inability to improve in both simultaneously.
00:33:31.18 Does this carry over to the virus world is an intriguing question.
00:33:35.18 We addressed it first in a phage called phi-6 that infects a bacterium known as Pseudomonas.
00:33:42.01 Pseudomonas syringae.
00:33:43.10 So, this bacterium is important in plant pathology -- it causes plant disease -- but in the laboratory
00:33:50.10 we merely use it to grow the phage as a resource, to examine how well does the phage evolve
00:33:56.12 in environments in the laboratory.
00:33:58.06 So, this is an RNA virus, so it has the capacity to undergo error rate at a high rate, and
00:34:05.04 this allows a lot of mutation and rapid change through time, and it has a very typical infection
00:34:10.11 cycle, where it infects a cell of the bacterium, bursts the cell for the progeny to be released,
00:34:16.11 and then they go on and infect more cells.
00:34:18.05 That's a lytic phase replication cycle.
00:34:21.23 This picture is showing how the virus is able to first infect cells, because the cells have
00:34:28.24 the structures that allow them to adhere to leaf surfaces and, in normal wild conditions
00:34:34.22 they would move across the leaf and enter into the plant, in order to do infection of
00:34:39.10 the plant.
00:34:40.10 So, through time, these viruses have evolved the ability to use those structures as the
00:34:45.08 thing that they attach to, through protein binding, to get into the cell.
00:34:49.13 And that's what's shown in the diagram.
00:34:51.24 So, one can first begin by examining a reaction norm, or just simply the capacity for phi-6
00:34:59.03 to grow under environmental challenges in the laboratory, and, even though those challenges
00:35:03.14 can be amazingly brief, only five minutes long in terms of heat shock, this diagram
00:35:09.14 is showing how the survival of a virus population of phi-6, relative to different heat shock
00:35:17.02 temperatures, a high degree of mortality starts to kick in well above the normal incubation
00:35:22.14 temperature in the laboratory of 25 C. When you get out to values greater than 40 C, you
00:35:29.07 find that this is highly impactful and deleterious to the viruses and their ability to thrive.
00:35:34.20 So, this is indicating how, in the absence of anything else, you can take this virus,
00:35:40.13 expose it to high heat, and, if the heat is high enough, it leads to a high degree of
00:35:45.04 mortality in the virus population.
00:35:47.17 Key in on both 45 and 50 C, where these are environments that we've manip. manipulated
00:35:53.22 in the laboratory to examine, how do viruses deal with heat shocks through time if they
00:35:59.18 see them, and can they key in on this high heat that leads to high mortality and become
00:36:05.16 better adapted to thriving in the face of heat shock?
00:36:10.01 This is a diagram from a recent paper, where it's simply showing you a typical experimental
00:36:13.22 design for a study like this.
00:36:16.03 If you just take the virus, such as in a test tube, in the absence of any cells, and you
00:36:21.03 put it in a heating block so that it'll be challenged with five minutes of high heat,
00:36:26.04 you can then take the viruses and grow them under normal low-heat conditions, where they
00:36:30.13 can replicate in the presence of bacteria, gather all that up, remove the cells, and
00:36:36.24 keep churning them through the experiment.
00:36:39.10 In this way, we're not worried about whether they can, say, co-evolve with the host bacteria
00:36:45.14 we're mostly keying in on the thing that causes high mortality -- the heat shock.
00:36:50.05 Can they key in on that and become better at thriving and improve this value, which
00:36:56.19 shows their very strong mortality that they suffer under high-heat environments?
00:37:02.01 Going quickly to the data from a paper where we did such an experiment, we find that thermal
00:37:07.16 tolerance, or heat shock selection, can readily occur in these viruses, and this is indicative
00:37:13.22 of something that we would call environmental robustness.
00:37:16.13 So, what is the ability of some population to thrive across different environments, and
00:37:22.14 maintain high fitness?
00:37:24.02 You'll see that the lineages shown in red, those that came out of an experiment where
00:37:28.09 this virus saw intermittent heat shocks at 50 C, these lineages improved way out at this
00:37:36.07 temperature, and you'll see this through a statistical result, that they do grow better
00:37:41.20 than their ancestral virus at that very high temperature.
00:37:45.05 Now, it's not like they have absolute capacity to shrug off that heat shock, but they do
00:37:50.07 have greater capacity to do so.
00:37:52.16 And, interestingly, you can see how there's a huge effect at the lower temperatures, which
00:37:57.15 ordinarily are degrading the wild type or unevolved virus, and now these lineages that
00:38:03.04 saw only 50 C have a great capacity to thrive at very, very warm temperatures and including
00:38:10.01 the highest temperature that they saw in the experiment.
00:38:13.17 How does this occur?
00:38:15.10 We've done several experiments of this type and always, for this virus, the same key mutation
00:38:21.06 is the first one and the most important one that leads to thermal tolerance evolving.
00:38:28.01 phi-6 has a genome that's split up into three different segments called large, medium, and
00:38:34.05 In this diagram, it below shows that we know what all the genes are and we know basically
00:38:37.12 what their functions.
00:38:39.04 And here we have a diagram, a cut-through, of the virus body plan that shows you that
00:38:43.20 that. all that nucleic acid is at the center of the virus and it's surrounded by a protein
00:38:49.23 But, uhh. cystoviruses -- this is the family that phi-6 belongs to -- they're are a little
00:38:54.20 different than other bacteriophages in that they have a lipid coat around the entire shell.
00:39:00.12 So, it's a pretty elaborate body plan for a phage, but I really only want you to understand
00:39:06.01 that the key mutation that provides thermal tolerance always seems to arise first on the
00:39:11.06 small segment, and it always seems to arrive in this lysin gene, which is we. going to
00:39:16.24 be responsible for virus particles both getting in and out of the cell, and it is always the
00:39:23.00 same mutation, V207F.
00:39:26.04 It's an amino acid substitution that I'll talk about further.
00:39:29.24 V207F seems to be the key mutation that always allows the viruses to evolve thermal tolerance.
00:39:36.13 And, mechanistically, this makes sense, because when you look at the structure of this lysin
00:39:42.03 protein, a very important enzyme, phenylalanine as an amino acid substitution fills a hydrophobic
00:39:49.06 pocket, and this makes the protein more stable under high heat.
00:39:53.22 So, this is only one mutation coming in but it has profound significance for the thing
00:39:59.10 that is causing high mortality in the virus populations.
00:40:03.03 It's a very simple explanation of how a single amino acid substitution can lead to a profound
00:40:09.15 ability to thrive under a key environmental challenge.
00:40:12.19 So, now, I will talk about how the reproduction is affected for this virus -- even though
00:40:20.15 the key mutation allowed better survival, it's detracting from reproduction.
00:40:25.00 So, if we look at, how does this V207F mutant thrive in an ordinary environment, 25 C, and
00:40:33.03 its ability to grow on bacteria, this diagram is first showing how the plaques. in other
00:40:38.22 words, when you take a virus and you grow it on a bacterial lawn, which is the background
00:40:44.15 in this diagram in white, each one of the particles, if they hit the lawn independently,
00:40:49.18 they'll infect a cell and the progeny will exit that cell, infect neighboring cells,
00:40:54.23 and eventually you'll get this hole in the bacterial lawn called a plaque.
00:40:58.17 Well, something interesting happens when you look at the morphology of the plaques of the
00:41:03.03 wild type virus, which is heat-sensitive, versus this V207F mutant that is heat-tolerant.
00:41:09.19 In all cases, the V207F mutant makes this weird-looking plaque that has a bull's-eye.
00:41:16.11 bull's-eye morphology to it.
00:41:18.09 So, that must be that cells missed being infected and killed as that plaque was produced on
00:41:25.10 the lawn, otherwise it wouldn't have that grayish appearance.
00:41:28.02 In other words, it is not as effective at killing cells even though it is thermal tolerant.
00:41:34.07 That's shown in the bar graph, here, where the selection coefficient or "little s" that
00:41:39.13 is associated with this one mutation has a huge deleterious value under normal growth
00:41:46.21 The wild-type relative to itself, of course, grows equally well so we give it a value of
00:41:52.03 1, whereas the value for the thermal-tolerant mutant is a value much, much lower than 1,
00:41:58.12 and has a negative selection coefficient of 0.25.
00:42:03.00 In comparison to the data I showed you earlier, it's very evident that a life history trade-off
00:42:08.04 is occurring in this virus.
00:42:09.17 In other words, it can either invest in better survival, but the problem is this leads to
00:42:16.17 lower reproduction.
00:42:18.11 This is echoing something that we see in cellular systems, with the investment in either survival
00:42:23.05 or reproduction, but not both at the same time occurring simultaneously.
00:42:29.07 It also relates to an earlier study, where the researchers found that if you just randomly
00:42:35.02 take viruses that can infect a different bacterium -- E. coli -- and you look at what is their
00:42:40.13 mortality rate versus their multiplication rate, and you plot that on the same graph,
00:42:45.17 there's a pretty amazing relationship for these viruses that they produced in their
00:42:49.20 study or used in their study to show that these are highly correlated traits to one
00:42:56.13 So, either these viruses that they studied grew well and survived poorly, or had a high
00:43:01.09 mortality rate, or they grew poorly and survived better.
00:43:05.10 So, it shows that if you just look at viruses from the natural environment and you look
00:43:11.13 at their relationship for survival versus reproduction, they show a big difference,
00:43:16.22 and they fall along this line.
00:43:18.24 You can think of our experiment as having taken any one virus on this line, and can
00:43:23.17 you move it up or down the line through an experimental evolution study, and that's exactly
00:43:27.24 what we did.
00:43:28.24 So, the survival reproduction trade-off holds, and you can move them up and down the line
00:43:33.24 if you vary the environment in the right way.
00:43:36.16 So, the bull's-eye plaque that I showed you before is a pretty strange morphology.
00:43:43.19 And there's actually. even though people have used old microbiology methods to the
00:43:47.16 current day, the ability to visualize plaques is something that has dated back to at least
00:43:52.23 the 1940s, so it's an old method, and yet we actually don't know very much mathematically.
00:43:58.15 If you construct a model about, how does a plaque form, this is still a pretty big challenge
00:44:03.04 to mathematical biologists.
00:44:05.05 The three-dimensionality that this plaque is growing in, on an agar surface, is something
00:44:10.07 that. it's very hard to describe mathematically.
00:44:12.13 And, especially if one looks through a time-lapse film of these types of bull's-eye plaques
00:44:19.02 forming, this is a very strange morphology that it's hard to understand how some cells
00:44:24.19 are killed initially, and then there's a lot of cells that do not get killed, and then.
00:44:29.10 and then more cells get killed, and so on, to lead to such a complex morphology.
00:44:33.13 I would say that this is still an ongoing challenge to simply describe how do plaques
00:44:38.07 form, mathematically and mechanistically.
00:44:40.22 In this example from our experiment, even one mutational change can lead to very different
00:44:46.00 morphology that provides an even bigger challenge to describe.
00:44:50.08 So, now, we can think of the viruses and the way that they encounter challenges in the
00:44:57.12 natural world as, yes, they have an amazing capacity to see challenges and overcome them.
00:45:05.01 So, we do fear emergence of viruses as something that will continue to be a challenge for humans,
00:45:11.23 domesticated species, conserving endangered species. all of these realms are threatened
00:45:17.24 by the emergence of viruses coming in and doing destruction.
00:45:21.14 However, there are certain environments where these champions of adaptation simply cannot
00:45:26.11 make it.
00:45:27.12 So, consistent with certain climate change.
00:45:29.14 climate change models, we have environmental change through time as something that can
00:45:33.16 constrain virus evolution, and some of the fundamental trade-offs that we see in cellular
00:45:38.13 systems, especially survival versus reproduction, carries over even into organisms that don't
00:45:45.07 undergo metabolism -- the viruses -- so it's not just they're shunting energy into one
00:45:49.16 thing or another.
00:45:51.01 It shows you more of a fundamental divide in the biological world of, can you invest
00:45:55.20 in survival versus reproduction, and get away with a co-investment in both of them?
00:46:00.07 And it seems like that's not the case.
00:46:02.10 So, I'd like to end by acknowledging the people who did this work.
00:46:06.11 I keyed in on a lot of the work done by my current lab group, as well as past lab members
00:46:10.24 who I've had the pleasure of working with.
00:46:12.20 I've had fantastic mentors and collaborators all over the world.
00:46:17.16 And I have to thank them deeply for their dedication to the experiments to present the
00:46:21.13 data that wound up in our papers.
00:46:23.22 I can also thank the funders for the work, NSF and its programs such as the BEACON Center
00:46:31.09 for experimental evolution, as well as NIH, Yale University, and nonprofits such as the
00:46:38.02 Project High Hopes Foundation have provided key funds for all the work that I showed you
Animal Models Used in Hepatitis C Virus Research.
<p>The narrow range of species permissive to infection by hepatitis C virus (HCV) presents a unique challenge to the development of useful animal models for studying HCV, as well as host immune responses and development of chronic infection and disease. Following earlier studies in chimpanzees, several unique approaches have been pursued to develop useful animal models for research while avoiding the important ethical concerns and costs inherent in research with chimpanzees. Genetically related hepatotropic viruses that infect animals are being used as surrogates for HCV in research studies chimeras of these surrogate viruses harboring specific regions of the HCV genome are being developed to improve their utility for vaccine testing. Concurrently, genetically humanized mice are being developed and continually advanced using human factors known to be involved in virus entry and replication. Further, xenotransplantation of human hepatocytes into mice allows for the direct study of HCV infection in human liver tissue in a small animal model. The current advances in each of these approaches are discussed in the present review.</p>
Scientists classify viruses based on how they replicate their genome. Some virus genomes are made of RNA, others are made of DNA. Some viruses use a single strand, others use a double strand. The complexities involved in replicating and packaging these different molecules places viruses into seven different categories.
Class I virus genomes are made of double stranded DNA, the same as the human genome. This makes it easy for these virus molecules to use the cell’s natural machinery to produce proteins from the virus DNA. However, in order for DNA polymerase (the molecule which copies DNA) to be active the cell must be dividing. Some Class I virus molecules include sections of DNA which make the cell actively start dividing. These virus molecules can lead to cancer. Human papilloma virus is a sexually-transmitted Class I virus, and can cause cervical cancer.
A Class II virus contains only a single strand of DNA. Before it can be read by the host’s DNA polymerase enzymes, it must be converted to double stranded DNA. It does this by hijacking the host cell’s histones (DNA proteins) and DNA polymerase. Instead of waiting for the cell to divide or forcing it to, Class II virus DNA contains coding for a protein called Rep. This replication enzyme replicates the original single-stranded virus genome. Other proteins are created from the DNA and used to create protein coats with the cellular machinery. The single-stranded DNA is then packaged into these protein coats, and new virus packages are created.
Class III virus genomes are created from double-stranded RNA. While this is unusual, these virus packages come with their own protein, RNA polymerase. This protein can create messenger RNA (mRNA) from the double-stranded virus RNA. The virus RNA therefore stays within the virus capsule, and only the mRNA enters the cytoplasm of the host. Here, the mRNA is converted into proteins, some of which include more RNA polymerase. This RNA polymerase creates a new double-stranded RNA, which is encapsulated by the proteins and released from the cell.
Class IV viruses are single-stranded RNA, almost identical to mRNA produced by the host cell. With these viruses the entire protein coat is engulfed by an uninfected host cell. The small RNA genome escapes the protein coat, and makes its way into the cytoplasm. This one mRNA-like strand codes for a large polyprotein, which will be created by the hosts ribosomes. The polyprotein naturally breaks into different parts. Some create protein coats, while others read and replicate the original strand of viral RNA. The virus continues to replicate and create new, fully packed virus particles. When the cell is completely full, it ruptures and releases the virus particles into the blood or environment. Up to 10,000 virus particles can be release from a single cell.
The virus genomes in Class V are also single-stranded RNA. However, they run in the opposite direction from normal mRNA. Therefore, the cell’s machinery cannot read them directly. These virus molecules contain a RNA polymerase molecule which can read in reverse. These virus molecules have large capsules, surrounded by cell membrane and proteins. When the virus approaches a cell, its membrane proteins bind with the cell, and it is drawn into the cytoplasm. Here, it breaks apart, releasing the backwards viral RNA and associated proteins. These small complexes produce regular mRNA, which creates new virus complexes. These unfinished complexes move to the cell surface, where they line the cell membrane with proteins they create. When they are finished, they wrap themselves in this membrane, and tear away from the cell.
Class VI virus genomes are the same as Class V, but they use a different method to replicate. Class VI virus particles are known as retroviruses. Instead of creating mRNA from the viral RNA, these virus molecules work with a different protein. Known as reverse transcriptase, this enzyme is able to create DNA from the virus RNA. In doing so, the viral RNA is converted to double-stranded DNA. This DNA then produces new virus. The DNA can incorporate with the host DNA, and in doing so become endogenized. This means that the DNA will remain in the cell as long as the cell lives. If the cell is found in a germ line, such as a sperm or egg, the virus will permanently become a part of the host’s genome. It is estimated that 5-8% of the human genome is left over retrovirus DNA.
The final class, Class VII, includes the pararetroviruses. Similar to Class VI, these virus genomes use reverse transcriptase. However, these virus genomes are package as DNA, not RNA. These viruses insert themselves directly into the host genome, which begins transposing the viral DNA into RNA. Most of this RNA will be mRNA, used to create a polyprotein. Part of the polyprotein is reverse transcriptase. This reverse transcriptase works on pieces of RNA known as pregenome. It reads these RNA molecules and produces the original virus DNA. This is then packaged into viral protein coats. Class VII viruses are often found in plants, and can travel between cells using the plasmodesmata, or they can be carried by herbivorous insects feeding on the plants. Aphids carry many plant diseases, as their proboscis pierces plant cell walls and they drink the cytoplasm.
Virology is a Specialty Section devoted to communicating cutting-edge research on Human/Animal Viruses and Phages and the interactions with their hosts. The mission of Virology is to publish significant findings that impact the specialty of Virology as a whole, and it attempts to go beyond incremental reports focused on a particular virus. This Specialty Section accepts article submissions on major advancements in the understanding of viruses that infect bacteria, archaea, fungi or animals, and strives to cover topics both basic and applied. In particular, we welcome papers that focus on the molecular, cellular or structural biology of virus-host interactions, virus replication/gene expression, bacterial, archaeal, fungal and animal model studies of virus infections, viral populations and evolution, epidemiology, drug/vaccine development against animal viruses. Using the innovative Frontiers peer review, our major purpose is to accelerate scientific communication and stimulate research activity in the specialty of Virology and related areas.
Areas covered: Virus replication strategies virus intracellular movement and transit between cells structural biology of viral proteins and genomes viral pathogenesis innate and acquired immunity against viruses evolution and epidemiology of viruses, emerging viruses virus vectors antiviral agents and subviral pathogens.
Quantitative analyses need to be performed on a minimum number of 3 biological replicates in order to enable an assessment of significance. This includes quantitative omics studies (transcriptomics, proteomics, metabolomics) as well as phenotypic measurements, quantitative assays, and qPCR expression analysis. Studies that do not comply with these replication requirements will not be considered for review.
Studies falling in the categories below will also not be considered for review, unless they are extended to provide novel and meaningful insights into gene/protein function and/or the biology of the virus:
&bull Comparative transcriptomic analyses that report a collection of differentially expressed genes, some validated by qPCR under different conditions or treatments
&bull Descriptive studies that merely define gene families using basic phylogenetics and assign cursory functional attributions (e.g. expression profiles, hormone or metabolites levels, promoter analysis, informatic parameters)
&bull Studies that only describe new viral genome sequences accompanied with basic phylogenetic analyses