How Viruses Replicate and Change

Question 1

T/F: Viruses use many host cellular products for replication; they are NOT good targets for antivirals

Answer 1

True

Question 2

In regards to the attachment step in viral replication, viruses bind to…

Answer 2

cellular receptors on the host cell

Question 3

In regards to the attachment step of replication, what is HIV’s primary receptor?

Answer 3

CD4

CCR5 or CXCR4 are secondary receptors

Question 4

In regards to the attachment step of replication, what does Influenza use as its receptor?

Answer 4

Sialic acid

Question 5

What cells have these viral receptors help determine….

Answer 5

the tropism of the virus or, put another way, what kind of cell the virus can infect

Question 6

If a cell does not have the viral receptor….

Answer 6

the virus cannot infect the cell. Therefore, the viral receptor helps determine what cells the virus can infect or the tropism of the virus

Question 7

There are other determinants of tropism other than receptors. Give an example:

Answer 7

Some viruses can enter certain cells, but if the cells are missing a cellular factor required for viral replication, the virus will not be able to replicate

Question 8

T/F: Tropism determines what type of cell the virus infects but not the species of animal the virus can infect.

Answer 8

FALSE - tropism determines not only what cell type the virus infects but also the species of animal the virus can infect.

This becomes important in zoonotic transmission.

Question 9

Entry at the cell membrane is mainly used for _______

Answer 9

enveloped viruses

Some enveloped viruses can fuse the lipid bilayer of the virus with the cell membrane. (Some naked viruses may make a hole in the cellular membrane for entry).

Question 10

T/F: Both enveloped and naked viruses can be endocytosed

Answer 10

TRUE - The lower pH of the endosome helps the virus enter the cytoplasm from the endosome. (The lower pH causes a conformational change of some viral proteins allowing the virus to escape the endosome).

Question 11

Where does most replication take place? What are some exceptions to this?

Answer 11

Nucleus

Exceptions:
-poxvirus –> cytoplasm
-HBV –> both nucleus and cytoplasm

Question 12

Give an examples of herpesvirus replication

Answer 12

(immediate early)
1) DNA into the nucleus
2) Host RNA pol II
transcribes early genes-transcription factors

(Early - now can make copies of viral DNA)
3) Second wave genes-Transcription factors and viral DNA polymerase
4) Viral DNA replication

(Late - lots of structural protein made)
5) Late gene production-Structural proteins made
6) Viral assembly in the nucleus/progeny virus

Question 13

Three DNA viruses do not make their own viral DNA polymerase; what are they?

Answer 13

Pappilomavirus
Polyomavirus
Parvovirus

Question 14

What do papillomavirus, polyomavirus, and parvovirus use to replicate their viral DNA?

Answer 14

Cellular DNA polymerase

This means that the cells need to be in the S-phase of the cell cycle for the virus to replicate

Question 15

Papillomavirus and polyomavirus can cause cell-cycle dysregulation by….

Answer 15

inhibiting pRb and making the cell go into cycle. Most of the time, this is not a problem as the cell dies. However, if the virus causes cell cycle dysregulation but does not kill the cell, there is a chance for the cell to become cancerous (hence cervical cancer with papillomavirus)

Question 16

_______ cannot cause the cell to enter the S-phase and must infect cells already replicating

Answer 16

Parvovirus

Question 17

Where do Poxviruses replicate?

Answer 17

In the cytoplasm, not the nucleus. They have a viral DNA-dependent RNA polymerase used to make messenger RNA

Question 18

Hepadnavirus HBV has a reverse transcriptase. Why is this important?

Answer 18

Because antiviral therapy for HBV infection targets the HBV reverse transcriptase. HBV replicates in both the nucleus and cytoplasm.

Question 19

Describe +ssRNA virus replication

Answer 19

1) The +ssRNA viruses can enter the cell and right away make protein. **Again, the first thing +ssRNA viruses do when they enter the cell is use the cell machinery to translate their +ssRNA into a large polyprotein (retroviruses are the exception)

2) They all need to cleave this polyprotein to make individual viral proteins. So, all +ssRNA viruses have a viral protease

3) They next need to make more RNA from their own RNA. The cell does not have any RNA-dependant RNA polymerase, so all RNA viruses need to make a viral RNA-dependant RNA polymerase (this protein is cleaved out of the viral polyprotein)

4) All +ssRNA viruses have a viral protease and a viral polymerase that are great targets for antiviral drugs

Question 20

________ are +ssRNA viruses that have two copies of the same genetic material

Answer 20

Retroviruses

Question 21

Why are retroviruses unique?

Answer 21

Because they make a DNA copy of themselves by using reverse transcriptase as part of their replication cycle. The reverse transcriptase is carries into the cell by the virus; it is in the virion

Question 22

Describe the rest of the Retroviruses replication cycle after it makes a copy of it’s own DNA

Answer 22

1) One they make a DNA copy of their genetic material, they integrate that copy into the host cell chromosome. That viral DNA copy is in the cell for the life of the cell

2) Retroviruses next use the cellular RNA polymerase to make viral messenger RNA from the integrated viral DNA. This viral mRNA travels to the cytoplasm, where it gets made into protein

3) Retroviruses still make a polyprotein that needs to be cleaved by a viral protease. In HIV, the viral protease cleaves the viral proteins after the budding of the virion. The protease helps mature the viral particle.

Question 23

Describe negative-sense RNA viruses replication (-ssRNA)

Answer 23

1) The most important thing to remember is that the first thing they do when they enter the cell is make mRNA from their -ssRNA. They do this using a viral polymerase that they carry into the cell with them in their virion

2) They do NOT need a viral protease because they make mRNA for each viral protein

3) They do require a viral polymerase that they bring into the cell in their virion

Question 24

_______ viruses are all helical and enveloped

Answer 24

-ssRNA

Question 25

__________ virus is a defective virus that MUST co-infect a cell with HBV to replicate

Answer 25

Hepatitis D

Question 26

What are the two types of large changes seen with antigenic shift?

Answer 26

Gene recombination
Gene reassortment

Question 27

What has to occur for gene recombination to take place?

Answer 27

For this to happen, two viruses of the same type infect the same cell. They might switch parts of their genome by recombination. This can result in several proteins being replaced at a time between the strains resulting in large change.

Question 28

What do you need for gene rassortment?

Answer 28

Need a segmented genome. Viruses with a segmented genome have many pieces of genetic material, with each piece encoding one to two proteins. All of the separate sections of genetic material need to be packaged into each virus to be infectious.

Question 29

Which viruses have a segmented genome?

Answer 29

BOAR virus families have segmented genomes

Bunyavirus
Orthomyxovirus
Arenavirus
Reovirus

Question 30

When talking about gene reassortment, when does reassortment happen? What is reassortment responsible for?

Answer 30

-Reassortment happens when two strains of the same segmented virus infect the same cell. The resulting viruses have segments from both infecting strains resulting in a very different virus from the parental strains

-Gene reassortment is responsible for the majority of influenza pandemics

Question 31

Different polymerases have different _______

Answer 31

fidelity; they have different error rates and ability to correct mistakes.

Question 32

In regards to antigenic drift mutation, list the mutation rate in order of lowest mutation rate to highest mutation rate for different polymerases

Answer 32

higher eukaryotes < prokaryotes < DNA viruses < RNA viruses (highest mutation rate)

Question 33

T/F: DNA viruses have higher mutation rates than RNA viruses

Answer 33

FALSE - DNA viruses have LOWER mutation rates than RNA viruses

Question 34

Most RNA viruses cannot ______

Answer 34

proofread.

A base inserted by mistake will not be corrected, leading to a higher mutation rate

Question 35

Describe viral Quasi-species

Answer 35

If you have a chronic infection, which allows the virus to replicate many times, you could have lots of different viruses in the body at ant one time (HIV and HCV) or put another way, many quasi-species of the virus.

-The ability of the virus to make single-nucleotide changes every 1-100 viruses made (depending on the virus) helps viruses to change rapidly with changing environmental conditions
-Most of these mutations will not be useful or will harm the virus and will not be passed on when a new person is infected
-(Remember, the virus that can replicate the best will be the predominant virus in the body. That is the virus that, more than likely, will be transmitted to a new person. Some viruses can withstand more changes than others or have a higher mutation rate. Therefore, these viruses will change more. All viruses will, however, acquire silent or conservative mutations over time. These mutations either do not alter the virus’s amino acids or make a
conservative amino acid change. So the sequence of the virus will subtly change over time with the accumulation of these mutations. Changes in the viral sequence are beneficial when tracking viruses in epidemiological studies of outbreaks.)

Question 36

T/F: It is possible in chronic infections, when antiviral therapy is started, a virus carrying a mutation resistant to the antiviral is already present

Answer 36

TRUE - this can be true for HIV and HCV and why combination therapy is so necessary