How Viruses Replicate

Question 1

Why are viruses not good targets for antivirals?

Answer 1

because viruses use many host cellular products for replication and we can’t target at own’s cell machinery

Question 2

What is HIV primary and secondary receptors?

Answer 2

primary: CD4
secondary: CCR5 and CXCR4

Question 3

What is influenza’s primary receptor?

Answer 3

sialic acid

Question 4

What does tropism determine?

Answer 4

what kind of cell the virus can infect and species of animal the virus can infect (zoonotic transmission)
- if a cell does not have the viral receptor, the virus can NOT infect the cell
- sometimes, viruses can enter certain cells, but if cell is missing a cellular factor required for viral replication, virus won’t replicate

Question 5

T/F: If primary and secondary receptors, only one has to be present

Answer 5

False!
Both must be present to infect cell

Question 6

What are the 2 modes of entry for viruses?

Answer 6

• enveloped viruses can fuse the lipid bilayer of virus with cell membrane (some naked viruses can make a hole in cell membrane for entry)
• both enveloped and naked can be endocytosed. lower pH of endosome helps virus enter cytoplasm from endosome by causing conformational change of some viral proteins

Question 7

What is uncoating?

Answer 7

release of genetic material from the virus

Question 8

Where does most virus replication take place? What are the exceptions?

Answer 8

• mostly: nucleus
• exceptions:
  poxvirus- cytoplasm
  HBV- both nucleus and cytoplasm

Question 9

What is the virus replication process of herpesvirus?

Answer 9

1) DNA into nucleus
2) Host RNA polymerase II transcribes early gene transcription factors
3) Second wave gene: transcription factors and viral DNA polymerase
4) Viral DNA replication
5) Late gene production- structural proteins made
6) Viral assembly in nucleus/progeny virus

Question 10

What DNA viruses have no viral DNA polymerase?

Answer 10

• papillomavirus
• polyomavirus
• parvovirus
• requires the cell to be in S phase of cell cycle for virus to replicate

Question 11

What viruses can cause cell-cycle deregulation by inhibiting pRb and making the cell go into cycle?

Answer 11

• papillomavirus
• polyomavirus
  most of the time, this isn’t a problem but if the cell isn’t killed it can become cancerous (commonly seen in papillomavirus- HPV 16&18)

Question 12

What virus cannot cause the cell to enter the S-phase and must infect cells already replicating?

Answer 12

• Parvovirus
  replicates in erythrocyte progenitor cells and can cause anemia

Question 13

How do papillomavirus, polyomavirus, and parvovirus replicate without viral DNA polymerase?

Answer 13

1) DNA into nucleus
2) Host RNA polymerase II transcribes early gene transcription factors
3) Need an actively dividing cell to replicate their viral DNA
4) Viral DNA replication
5) Late gene production- structural proteins made
6) Viral assembly /progeny virus

Question 14

What viruses use their own viral polymerases to make more genetic material?

Answer 14

• Adeno
• Herpes
• Pox
• Hepadna

Question 15

Which DNA virus replicates in the cytoplasm?

Answer 15

poxviruses
- have a viral DNA-dependent RNA polymerase used to make messenger RNA

Question 16

Which DNA virus replicates in both nucleus and cytoplasm?

Answer 16

hepadnavirus (HBV)
- has reverse transcriptase which is important for antiviral therapy for HBV infection targets the HBV reverse transcriptase

Question 17

What is mRNA the same as?

Answer 17

+ssRNA

Question 18

What are the steps of RNA virus replication?

Answer 18

• +ssRNA virus enters cells and right away makes protein making a large polyprotein (exception retroviruses)
• cleave polyprotein to make individual viral protein via viral protease
• make a viral RNA-dependent RNA polymerase that was cleaved out of polyprotein

Question 19

What does +ssRNA viruses have that make them great targets for antiviral drugs?

Answer 19

• viral polymerase (made from cleavage of polyprotein)
• viral protease

Question 20

What are retroviruses?

Answer 20

• +ssRNA viruses have 2 copies of same genetic material
• unique because make a DNA copy of themselves by using reverse transcriptase as part of replication cycle

Question 21

How do retroviruses make the polyprotein?

Answer 21

• retroviruses use cellular RNA polymerase to make viral messenger RNA from the integrated viral DNA
• this viral mRNA travels to cytoplasm to get made into protein
• the polyprotein is cleaved by a viral protease which helps mature the viral particle

Question 22

What takes reverse transcriptase into the cell in retroviruses?

Answer 22

virion
- only they make a DNA copy of their genetic material, they integrate that copy into host cell chromosome and the viral DNA copy is in the cell for the rest of the cell’s life

Question 23

In -ssRNA viruses, what is the first thing they do when they enter the cell?

Answer 23

make mRNA from their -ssRNA using viral polymerase that they carried with them in their virion
- SO, they do NOT need a viral protease because they make mRNA for each viral protein
- DO require viral polymerase

Question 24

What is characteristic of -ssRNA viruses?

Answer 24

all helical and enveloped
(all other RNA viruses are icosahedral)

Question 25

How do -ssRNA viruses make mRNA?

Answer 25

- use their -ssRNA - **viral polymerase** is carried into the cell in their virion - **do NOT require viral protease**

Question 26

Why is Hepatitis D virus (-ssRNA) defective?

Answer 26

HBV is required for HDV to replicate

Question 27

What RNA virus makes a polyprotein when it enters the cell?

Answer 27

+ssRNA

Question 28

What is antigenic drift?

Answer 28

- small changes - mutation - happens with every virus

Question 29

What is antigenic shift?

Answer 29

- large changes - gene recombination/reassortment - seen in pandemics

Question 30

Which are the exceptions for virion assembly in the nucleus of DNA viruses?

Answer 30

- poxvirus - hepadnavirus

Question 31

What is required in genetic recombination?

Answer 31

- requires 2 very similar viruses to infect the same cell - results in several proteins being replaced at a time between strains resulting in a large change

Question 32

What is required in genetic reassortment?

Answer 32

- segmented genome - ex: BOAR viruses

Question 33

Order the mutation rate from lowest to highest in regards to antigenic drift:

Answer 33

higher eukaryotes (lowest) < prokaryotes < DNA viruses < RNA viruses (highest)

Question 34

Why are RNA viruses more likely to have a higher mutation rate?

Answer 34

because most RNA viruses cannot proofread *(a base inserted by mistake will not be corrected)*

Question 35

What is a viral quasi species?

Answer 35

- bunch of similar but not identical viruses in a host due to high mutation rate during replication - especially seen in RNA viruses (HIV)

Question 36

T/F: Most mutations in viruses are helpful for virus and can spread in population

Answer 36

False! Most will actually harm the virus and not be passed onto when a new person is infected/ *viruses that are infective for a long time like HIV are more prone to mutation and be beneficial to the virus and can spread through a population*

Question 37

Why do antiviral therapies sometimes not work (especially in HIV)?

Answer 37

- it's possible that when an antiviral therapy is started, a virus was carrying a mutation that was resistant to the antiviral - this is why combination therapy (2-3 different classes of drugs) is necessary in HIV and HVC