Retroviruses

Question 1

What are the kinds of infections caused by retroviruses?

Answer 1

no illness
tumors
wasting diseases, neurological
immune deficiencies (HIV)

Question 2

Properties of retroviruses

Answer 2

acquire host cell sequences that could be oncogenes
integrate into host cell chromosomes
fast genome evolution

Question 3

retroviruses’ structure

Answer 3

enveloped with envelope proteins in membrane, matrix proteins underneath lipid bilayer

capside of structural proteins

2 copies of + sense ssRNA

core can be differently shaped

Question 4

How is retroviral genomic RNA made?

Answer 4

by host’s polymerase II

Question 5

Retrovirus genomic RNA composition

Answer 5

from 5' to 3':
5'cap
R: repeat
U5: unique for 5 end
gag gene: encodes polyprotein consisting of matrix, capsid, nucleocapsid, and protease

pol (polymerase) gene: reverse transcriptase, integrase

env (envelope) gene: encodes env protein which gets cleaved to surface (SU) and transmembrane (TM) portions

U3: unique for 3’ end

R: second repeat

3’ poly A tail

Question 6

Difference btwn simple retrovirus and complex?

Answer 6

Complex retrovirus does alternative splicing with additional genes; simple only splices once

Question 7

replication cycle of retrovirus

Answer 7

adsorption
penetration, uncoating
reverse transcription
goes into nucleus
integrates into host DNA
viral RNA synthesis using host pol II
RNA processing
virion protein synthesis
assembly and buds
capsid matures

Question 8

What steps of replication cycle does retrovirus use host cell machinery a lot?

Answer 8

after integration

Question 9

How does retrovirus bind cell?

Answer 9

envelope protein and host cell receptor

Question 10

What is used to convert ssRNA to dsRNA for the retrovirus?

Answer 10

reverse transcriptase

Question 11

Does HIV genome get into the nucleus?

Answer 11

Yes

Question 12

How is the ssRNA genome from the retrovirus different from the dsRNA provirus?

Answer 12

dsRNA provirus is longer than template RNA b/c it contains U3 and U5 duplicated at ends to make LONG TERMINAL REPEATS (LTRs)

Question 13

Reverse transcriptase has two polymerase activities. Name them

Answer 13

RNA dependent DNA polymerase

DNA dependent DNA polymerase

Question 14

What explains the rapid evolution of the retrovirus genome?

Answer 14

reverse transcriptase makes 5 errors per genome

Question 15

What is a very important target for antiviral drugs against HIV?

Answer 15

reverse transcriptase

Question 16

Where does integrase choose to integrate the retrovirus dsDNA?

Answer 16

it is not specific–insertion occurs at random

Question 17

What does integrase recognize with the retroviral DNA?

Answer 17

ends of U3 and U5

Question 18

How long does the integrated retroviral DNA stay in the host cell’s DNA?

Answer 18

forever

Question 19

What is the major role of the long terminal repeat in retroviral DNA?

Answer 19

directs viral RNA synthesis because U3 has sites for cellular transcription factors

Question 20

Why is HIV active in activated T cells?

Answer 20

activated T cells have the transcription factor NFkB, which the HIV LTR needs

Question 21

In what kinds of retroviruses does splicing of envelope mRNA occur?

Answer 21

all retroviruses

Question 22

Why is targeting mRNA splicing in retroviruses not good?

Answer 22

host cell also uses the machinery for splicing

Question 23

How is gag-pol of the retrovirus translated?

Answer 23

ribosomes ignore the gag stop codon and go on to the end of pol

Question 24

What cleaves the original envelope protein of retroviruses into two smaller fragments?

Answer 24

protease

Question 25

Why is cleavage of envelope protein of retroviruses important?

Answer 25

because without it, the gp160 cannot fuse with a cell to infect a cell

Question 26

How do we select for viral unspliced RNA in packaging a retrovirus? (instead of envelope spliced RNA)

Answer 26

unspliced RNA has a psi signal

Question 27

When does proteolysis of gag and gag-pol by protease occur?

Answer 27

after budding

Question 28

How do non-transforming retroviruses cause cancer?

Answer 28

viral genome inserts at an inappropriate place in the host genome, causing disturbances in regulation

Question 29

how do transforming retroviruses cause cancer?

Answer 29

tumors within weeks

the viruses have a mutated cellular gene