Virology Test 2: Short Answer and some multiple choice

Name the three subfamilies of herpesviridae and examples listed in the slideshow

-Alpha: herpes simplex types 1 and 2; Varicella zoster virus (aka chicken pox)-rather common infections -Beta: cytomegalovirus and herpes virus types 6/7-commonly infected but usually no problems -Gamma: Epstein-Barr and Kaposi's sarcoma-associated virus (herpesvirus type 8)-oncolytic viruses

Groups or categories of people that would be considered as immunocompromised are...(would be good to explain why they are)

-Children/Babies: the immune system is built up over one's lifetime. Since children and babies are rather young, they have just not had as much exposure to pathogens as adults. Thus, they are immunocompromised -Elderly: the immune system tends to wane in response time and strength as one ages. The elderly are more susceptible to pathogenic disease as their immune response will not be as strong -Autoimmune disorders: they are born or acquire an autoimmune disease where the immune system is attacking them or the immune system is compromised anyway -Transplant or chemotherapy recipients: have to knock down the immune system or decrease response to avoid rejection and treat body with drugs to kill cancerous agents. Both decrease the strength of the immune system

Describe some anti-viral activities that are mediated by IFN-alpha and IFN-beta

-Helps to activate genes that encode antiviral proteins like protein kinase R and Rnase L (targets dsRNA) -Induce apoptosis if infected -Activate NK cells -Increase antigen processing and presentation of MHC class I for presentation to CD8 T cells

While _____________ helps to activate NK cells, upon their activation, NK cells will release __________ to stimulate antigen presentation and activating phagocytic cells.

-IFN alpha -IFN gamma

There are many ways that a virion can budd and be released from the host cell. Describe ways the virion can initiate budding and where it can bud from.

-May utilize virally encoded enzymes to cleave the virion from the membrane. An example of this is how neuramidase is needed to free the flu virions from a cell (think of tamiflu) -Virally encoded enzymes could destabilize the lipid bilayer for virions to bud (i.e. it breaks through the membrane) -Viruses that mature in the nucleus, such as herpesviruses, must bud from nuclear membrane and go to golgi complex for envelope -Hepadenaviruses bud into membrane compartment between ER and Golgi complex

Describe the steps to assemble an icosahedron virus (generally)

1. A procapsid or circular shaped "shell" is present/synthesized prior to genome addition 2. Either during or after genome insertion, the procapsid undergoes a structural or conformational change to take on the final icosahedron shape 3. Additionally, genome can be added to the procapsid via channels at the site that will become a vertice of the icosahedron

Describe the four kinds of polymerases a virus can use for genome replication and describe which Baltimore class viruses would utilize that polymerase

1. DNA-dependent DNA-polymerase (DdDp): used by both Class I and Class II 2. RNA-dependent RNA-polymerase (RdRp): used by Class III, VI, and V 3. RNA-dependent DNA-polymerase (RdDp): used by Classes VI and VII 4. DNA-dependent RNA-polymerase (DdRp): used by both Class VI and VII; this is actually RNA polymerase I we use to make mRNA

For HSV-1, describe the process of how it attaches to the cellular membrane

1. Initially, it binds to a cell that has the heparan sulfate receptor 2. Secondary binding occurs via nectin and cell adhesion molecules 3. HSV-1 proteins, gB + gH/gL, help the virus with fuse with the cell's plasma membrane for entry

Summarize how herpesvirus assembles its virion and exits the cell (see pg. 128 if struggling)

1. Nucleocapsid acquires some of its tegument proteins in the nucleus 2. Nucleocapsid buds through the IM nuclear envelope to perinuclear space, acquiring a temporary envelope 3. Goes on to fuse with the OM of nuclear envelope to be released into cytoplasmic space 4. Rest of tegument proteins added 5. Receives its actual viral envelope via budding into a vesicle from the Golgi 6. Now enveloped, the virus in a golgi-derived vesicle is transported to the PM 7. Vesicle membrane fuses with the PM to release virion from the cell

When a virus goes into latency, what can happen to the DNA?

1. Viral genome gets incorporated into host cell genome and waits to be transcribed/come out (i.e. HIV) 2. Viral genome is maintained in an area separate from the host cell genome (extrachromosomal), like a bacterial plasmid

1. The components of the innate immunity include ___________________, ____________, ____________, and ____________. 2. The components of the adaptive immunity include ____________ and ___________. think mostly of cells

1. interferons; natural killer cells; phagocytic cells (macrophages); neutrophils 2. B cells; T cells (helper and cytotoxic)

Generally speaking, what is the role of interferons in the presence of a viral infection?

A cytokine that is produced in the presence of viral infections. They can detect viral genome, such as dsRNA and ssRNA (very unusual as cell doesn't produce dsRNA) to stop protein production (turn on antiviral genes) The outcome of interferon activation is that it can protect neighboring cells from getting infected or induced apoptosis

Describe the differences between a latent and productive infection. Be sure to explain why a virus would opt to undergo one over the other and provide examples, if necessary, of what kind of virus would use which one.

A latent infection is a non-active infection. That is, the virus is still within a host cell but not actively replicating its genome or synthesizing nucleic acids to any great extent. Viruses like HIV and herpes can go into latency. With HIV, the virus will replicate its genome and then insert into host...waiting. For Herpes, it causes a primary infection and then waits A productive infection is one where the virus is both replicating its genome and synthesizing its nucleic acids. There is a high level produced and spread in the host organism/cell. A virus can progress out of latency when it encounters a stimulus such as UV radiation or stress triggers

Dependovirus needs the help of........ to replicate

Adenovirus or Herpesvirus

The receptor for the B19 virus is...

Blood Group P antigen

Humoral vs. Cellular immune response

Both relate to the adaptive immune response Humoral: relates to B cells; antibody production for specific antigens Cellular: relates to T cells; viral presentation to T cells leads to differentiate into either helper T or cytotoxic T cells (depends on what MHC molecule)

What three structures define a herpesvirus virion?

Capsid (icosahedron), tegument, and envelope

What is fifth disease?

Caused by a parvovirus known as B19. The lysing of red blood cells is seen in children, giving a "slapped cheek" look.

For DNA viruses, what is the difference between conservative and semi-conservative replication?

Conservative: once daughter strands have been synthesized, parent strands go back together and daughter strands go back together Semi-conservative: once daughter strands have been synthesized, DNA is made up of one daughter and one parent strand together. This is seen in our DNA

ssDNA has a self-primer in the form of ______________. But, when the virus first enters the nucleus, ssDNA must be converted to _________.

DNA folded back on itself (complimentary) dsDNA

Defective particles are virus particles that were not packaged correctly. This means that the virion will be unsuccessful in causing an infection in a host cell. Why, then, would a virus intentionally decide to package defective particles?

Defective particles will still cause an immunogenic response in that the body will believe it is a working and possibly infectious particle. Thus, their release catches the attention of the immune system such that it wastes time attempting to catch defective particles. This is great for the infectious particles as they can sneak by or stay hidden from an effective immune response

Describe some situations where a latent virus can be induced to undergo replication

Eukaryotic cell goes to another phase of replication, irradiated by UV light, host organism becomes immunocompromised, or a second/helper virus infects the host cell

Regarding genome, what is special about the flu virus?

Even though it is a positive sense RNA virus, it goes into the cell nucleus for genome replication. It utilizes the cellular RNA as a primer for its replicative life cycle

True or False: As long as most proteins are assembled correctly for the herpesvirus virion, it will still be successful in establishing an infection.

False

Compare and contrast differences between a DdDp that is virally encoded vs. one that is cellular encoded

For a virally encoded DdDp, the virus would not need to go the nucleus as it already has its polymerase. Therefore, we should expect to see it replicate its genome in the cytoplasm. For a cellularly encoded DdDp, the virus would not encode the polymerase. Therefore, it would need to replicate its genome in the nucleus as that is where the replication machinery is located

HSV-1 vs. HSV-2

HSV-1: oropharyngeal, manifests as cold sores HSV-2: genital, seen as genital herpes

Explain what happens when the hepatitis B virus infects a host that already has hepatitis delta

Hepatitis delta is a satellite virus that needs the help of hepatitis B to cause an infection. It will tell hep B to stop synthesizing nucleic acids and genome to leave an "empty shell" of hep B. At this point, hep D can use the hep B virus surface proteins to coat and spread. There is no approved treatment for a hep D infection

There are cases where a virus and its host cell may co-evolve such that the host tolerates the presence of the virus. Explain what would happen if the virus entered an unfamiliar host.

If a virus and host cell have co-evolved, the virus itself may be in a latency phase where it is producing little to no genome replication or nucleic acids. While not the best situation, a host cell has learned to cope with the invader. On the other hand, a virus that transmits to another species via zoonosis does not have that kind of relationship established. This means that there will, most likely, be a high level of disease parthenogenesis or death as the virus goes into a productive infection

As a virus is attempting to package its genome into the virions, there are certain things it must overcome. Please describe some general challenges a virus may encounter.

If there are multiple segments, it must make sure that it puts each segment in the virion. Additionally, it would be best if there was no duplication. Since it is occurring in a crowded cellular environment, the virus must also avoid accidentally grabbing some host cell proteins and putting those in the virion as well

For circular DNA, there are two types of replication: rolling circle and theta. Describe how they both work

In rolling circle replication, the DNA being synthesized is constantly being "rolled off" of the parental strand such that genome replication is very quick. The enzyme does not even have to move off of the strand In theta replication, the synthesized DNA strand will separate as it is replicating to look like the "theta" greek letter. This is generally slower

How does the assembly of a helical virion work?

Involves coating copies of the genome with multiple copies of a protein (i.e. coat protein for tobacco mosaic virus or nucleoproteins for influenza). For TBV, the coat proteins form the discs of the coat protein and then assembly them on RNA for rod shape. -->makes virions and nucleocapsids

Why does HIV utilize MHC Class II molecules for its virion membrane?

It is to mimic or skew the immune system's response as the immune system may have difficulty determining if it is a pathogen. Additionally, it can be used so the virus can bind to other cells for entry, causing an infection

Generally speaking, what is the issue when a human is infected with Herpes B virus?

Its normal host is the macaque monkey so this would be a case of zoonosis. With a normal herpes infection, such as HSV-1 or HSV-2, the virus knows to go into latency in nerve cells so as to not cause problems for itself or the host. The problem with herpes B is that the virus will start to replicate in the nerve cells which is really not good. It could be that the virus isn't sure what to do in a new host or the host cannot control the virus. Either way, human infection of herpes B virus is fatal if not treated immediately as it leads to neurological damage and death.

How can a virus identify which proteins are its own to package into the virion?

Look for either a unique stretch of amino acids or create a secondary structure such as a loop. The secondary structure may be better as it is much easier for a virus to spot as opposed to random amino acids as there is a plethora of amino acids in a cell

Compare and contrast some general benefits and disadvantages of a virus that uses lytic or nonlytic release of virions from a cell

Lytic: good in that it can release a large amount of virions at one time. Not so great in that the lytic release catches the attention of the immune system (also causes a lot of cellular and tissue damage but only not good for host cell) Non-lytic: good in that it can hide from the immune system as the cell stays in tact to continue to produce virus. Does not create as much virus, not sure if that is a disadvantage or just noteworthy

In the viewpoint of herpesvirus, what is the advantage of establishing an infection in nerve cells?

Nerve cells never divide so it does not need to worry about constantly maintaining viral protein load. Additionally, nerve cells are considered to be "immunoprivileged". That is, they are mostly hidden from immune cells so its harder to detect/attack a virus that hides in nerve cells

Describe the purposes of the following enzymes involved with HSV-1 DNA replication. Ori-binding protein ssDNA-binding protein (SSBP) Helicase Polymerase processivity factor Primase DNA polymerase

Ori-binding protein: binds to an ori site on the virus to make DNA unwind at the site (initiates it); considered as a sort of helicase itself ssDNA-binding protein (SSBP): prevents the separated DNA strands from reannealing Helicase: known for unwinding or unzipping the DNA Polymerase processivity factor: complexes with the polymerase as a way to stabilize it for long nucleotide stretches. Primase: adds a primer sequence to the beginning such that DNA polymerase knows where to start DNA polymerase: responsible for adding complimentary nucleotides

What is the job of terminase for viruses?

Pump DNA into procapsid, recognize the packaging signal, and cleave the DNA (i.e. concatomers)

If a virus utilizes an RNA-dependent DNA polymerase for genome replication, its starting template is ____________ and it makes _____________. Additionally, what two classes would utilize this polymerase?

RNA; DNA Retroviruses and pararetroviruses

It has been said that retroviruses can be a key component of evolution. Explain why that is.

Retroviruses can reverse transcribe their genome into DNA and then implant it in the host cell genome. During this time, it is referred to as latency. At some point, the cell will transcribe the viral genome as well as the host cell genome to free the virus. Since retroviruses can be transmitted through different species and/or hosts, they may bring some DNA from the previous host as sort of a remnant of the host. Thus, we can look at evolution

Even though a virus that undergoes non-lytic release of virions does not causing lysing or bursting of a cell, we still tend to see a good amount of tissue damage from this kind of infection. Explain why that is

The immune system is able to detect that there is a virus present but it is hidden within the cells. Thus, it can try to initate an immune response with cytotoxic T cells, macrophages, neutrophils, and other phagocytic cells. The damage one sees from non-lytic viruses is not from the virus itself damaging the host but, rather, the host doing its best to eliminate the virus and causing collateral tissue damage from an overactivated immune response that is not very specific. This causes damage to nearby tissue that is not infected.

For retroviruses, describe the kind of polymerase(s) it uses and location (s) of genome repliation

The polymerase it uses has two different active sites such that one is a RNA-dependent DNA polymerase and then it will switch to a DNA-dependent RNA polymerase. In the cytoplasm, it uses the RNA-dependent DNA polymerase side to reverse transcribe its genome into DNA. Then, the virus will traverse to the nucleus and use the DNA-dependent RNA polymerase site to go back to its genome

While vaccines have seen much success in inducing a primary immune response, there are some viruses that we are unable to make a vaccine for. Give one reason why this is.

The purpose of a vaccine is to create things such as memory B cells that will remember and be quick to respond if the body happens to encounter the pathogen in the future. Unfortunately, there are some viruses that prevent any sort of memory formation. This means that vaccines are not helpful in that the B and T cells will have to start from scratch to attack the virus

When would a virus use theta replication and when would it use rolling circle?

Theta replication creates low level of DNA replication so a virus in latency would, most likely, opt to use this kind of replication. This is because the virus is not doing anything, actively, in latency so only a low level of replication is necessary. Once the virus is stimulated out of latency, it may go to sigma or rolling circle replication. This creates a significantly higher amount of DNA synthesized such that we have genome packaging.

Non-structural proteins do what to dsDNA (think in regards to how it began as ssDNA)?

They serve as a helicase to unwind the dsDNA and package only single strands into the procapsid

Upon testing someone for COVID, medical professionals saw that only IgM antibodies were present in circulation. What does this tell us about the length of their infection? Make sure to explain how you came to this conclusion.

This means that, at most, the person has only been infected for about two weeks. IgM is the first antibody class made in the body. If only IgM is circulating, this means the virus has not been in circulation that long or else the body would have had time to undergo somatic hypermutation and class switch. Thus, it is likely the researchers have caught this individual in the beginning of their infection.

True or False: Human cytomegalovirus is a common infection but, as long as you're not immunocompromised, does not cause problems

True

True or False: Toll like receptors (TLRs) recognize a wide variety of pathogen associated molecular patterns (PAMPs) for the innate immune response

True it can recognize lipids/lipoproteins/proteins/ LPS/flagellum

True or False: ssDNA viruses must convert their genome to dsDNA before it can replicate

True, it has to look like host cell DNA or else it will be unable to utilize the host cell machinery

True or False: viruses use proteins that are similar to histones used by host cells to tightly package their genome

True, referred to as supercoiling

VP16 is necessary for

Turning on the immediate early (IE) genes to begin replication

For the Baltimore classification of viruses, describe where we would expect the viral genome to replicate

Type I: its a dsDNA virus so it can replicate in the nucleus of a host cell Type II: these are both positive and negative ssDNA viruses. While they can replicate in the nucleus, typically, they must convert themselves into dsDNA to utilize the machinary Type III: dsRNA virus, replicates in the cytoplasm as it has no need to use cell machinery Type IV: + sense ssRNA, replicates in the cytoplasm Type V: - sense ssRNA, some replicate in nucleus while others replicate in the cytoplasm Type VI: retrovirus with + sense RNA; requires both the cytoplasm and nucleus to complete genome replication (RdDp in cytoplasm and DdRp in nucleus) Type VII: pararetrovirus with dsDNA, needs to use both the cytoplasm and nucleus for genome replication

CD4 T cells... (select all that apply) a. are called Helper T cells b. recognize MHC Class I molecules c. are responsible for killing virally infected cells d. secrete cytokines for B cell and cytotoxic T cell maturation

a and d

If the body has detected a virus lingering in the mucosal tissues, what type of immunoglobulin would you expect to see? a. IgA b. IgG c. IgM d. IgD

a. IgA

Which of the following describes an unusual feature/unique of a B19 virus infection in comparison to other viruses? a. Occurs in a bi-phasic infection b. disease is not commonly seen in humans c. Very small genome d. It produces concatomers

a. occurs in a bi-phasic infection

What is the purpose of... a. immediate early (IE) phase b. Early (E) phase c. Late (L) phase

a. transcription factor, gets everything going b. synthesizing of all the DNA that is required c. building the structural proteins for the virion to be packaged

CD8 T cells... (select all that apply) a. used to be called natural killer cells b. kill virally infected cells using perforins c. use similar methods as NK cells for killing d. recognize a peptide:MHC Class I complex

b, c, and d

If a dependovirus infects a host cell, but does not have its helper virus, what will occur? a. The dependovirus will not be able to withstand the host cell environment and be degraded by nucleases b. It will convert itself to dsDNA, integrate itself into the host cell genome, and establish a latent infection c. Hijack a host cell protein instead d. none of the above

b. It will convert itself to dsDNA, integrate itself into the host cell genome, and establish a latent infection

dsDNA are referred to as Class I viruses in the Baltimore classification. In comparison to our working knowledge of viral genomes, what is a puzzling feature of dsDNA genomes such as herpesvirus? a. It is a very large genome b. There is a lot of redundancy and introns c. Proteins can be highly variable d. No dsDNA viruses require the assistance of a helper virus to establish an infection

b. There is a lot of redundancy and introns

Cytomegalovirus is an example of a virus that comes out of latency because of.... a. UV irridation b. helper virus c. host becoming immunocompromised d. host cell entering mitosis

c. host becoming immunocompromised

If you were to observe a virus with only a small amount of cholesterol on its envelope, where should you conclude it budded from? a. Endoplasmic Reticulum b. Cellular membrane c. Nuclear membrane d. Mitochondria

c. Nuclear membrane

What kind of immune response can the coating of a virion with antibody have? a. Making the virion more attractive to phagocytosis via macrophages, neutrophils, and NK cells b. Activation of complement pathway to create the membrane attack complex, leads to cell death c. Antibody binds to receptors on virus and prevents it from attaching to host cell. This is a neutralization effect d. all of the above

d. all of the above

What kind of response would a good vaccine stimulate? a. cellular response only b. humoral response only c. formation of the membrane attack complex d. both cellular and humoral response

d. both cellular and humoral response

When looking at parvovirus, it uses _____________________ as its mechanism for DNA Replication. a. concatemers b. reverse transcription c. signal sequences d. rolling-hairpin

d. rolling-hairpin

Viruses go to the ____________ for glycosylation and then their nucleocapsid is attracted to _________________ because of _________________.

golgi membrane (could be cellular or other) high concentration of glycoproteins for its envelope

For an RNA virus, ____________ is typically stimulated but a DNA virus usually requires a _____________ response.

interferons; T cell mediated

Viremia

lots of viral load in the blood

How are the virions of ssDNA viruses released from the cell?

lysis (so much virus produced it causes the cell to burst)

Function of non-structural proteins vs. structural proteins (large and small mRNA strands, respectively)

non-structural: replication (enzymes) structural: making or building the viral capsid

Parvovirus uses __________________ to enter the cell

receptor-mediated endocytosis

For members of the herpesvirus family, concatemers are made during _____________________. Additionally, please describe what a concatemer is.

rolling circle replication Long stretches of DNA. Basically, you keep making exact copies of DNA, one after another without releasing any previously synthesized DNA. So, there are multiple copies of the virus genome

Compare and contrast the difference between self-assembly and directed assembly of a virus

self-assembly: can be assembled under purified components (protein and nucleic acid) under pH and certain ions. Relatively simple structure with only nucleic acid and one or a small number of protein species. RNA viruses, usually directed assembly: virions cannot reassemble their components in a test tube as they need the environment within the infected cell. May involved proteins that are temporarily present while under construction but not in mature virion. Scaffolding proteins

Describe the genome, virion shape, and size of parvoviruses

ssDNA, icosahedron, and rather small with only 18-26 nm long

Viruses can utilize a wide variety of primers to replicate its genome. Please describe some of these primers

ssDNA: can do self priming in that the DNA will fold back on itself to form some sort of loop. This requires the ssDNA to have complimentary base pairs to form the loop for the polymerase to begin replication. RNA primers: can be used, similar to living organisms. With this, a short stretch of RNA is added to where replication is supposed to begin as the polymerase looks for the 3' hydroxyl group Protein primers: unique to viruses. It can use a protein with a serine or threonine residue, utilizing the OH group for initiation of replication.

True or False: For the parvovirus genome, it does not matter if the (+) or (-) DNA strand is packaged

true