Retroviruses

Question 1

genome type

Answer 1

2 copies of (+)ssRNA with a dsDNA intermediate

Question 2

capsid structure

Answer 2

HIV = cone shaped

Question 3

enveloped?

Answer 3

enveloped

Question 4

What two factors enable recombination of retroviruses?

Answer 4

2 copies of (+)ssRNA
they are retrotransposons = integrates into host genome = can pick up new DNA

Question 5

Where does RT work?

Answer 5

RT begins in the capsid in the cytoplasm

Question 6

integrase (IN)

Answer 6

inserts dsDNA into host genome

Question 7

viral protease (PR)

Answer 7

required for maturation

Question 8

nucleocapsid vs capsid

Answer 8

NC coats viral genome
CA forms cone shell

Question 9

What are the 3 host dependency factors that are packaged

Answer 9

ICAM-1 assists in binding to target cells

tRNA-Lys is taken from the host and used as a primer for RT

Cyclophilin (CypA) modulates CA uncoating (timer for dsDNA release after RT)

Question 10

VAP and does it do fusion?

Answer 10

envelope (Env) and it also does fusion

Question 11

receptor and main coreceptor

Answer 11

Envelope (Env) binds CD4 and coreceptor CCR5

Question 12

How do we know that the co-receptor usage of HIV is critical for its infection?

Answer 12

Steve Crohn
CCR5(delta)32 mutation

Hetero = susceptible but slower progression
Homo = highly resistant

Question 13

Be familiar with the virus life cycle of retroviruses. You will not need to write this out from memory.

Answer 13

a. Env binds CD4 and CCR5
b. Env-mediated fusion at the plasma membrane. Conformation change causes fusion
c. RT begins in the capsid
d. Nuclear import of the entire capsid
e. Capsid uncoating in nucleus via CypA
f. dsDNA release into nuclus
g. dsDNA integrates into host genome via integrase
h. transcription and splicing
i. nuclear export of RNA
j. translation of viral proteins
k. assembly and budding
l. maturation

Question 14

Understand the four basic steps of reverse transcription

Answer 14

a. Host tRNA primer is packaged with the virus
b. RNA-dependant DNA synthesis (RT)
c. Ribonuclease H (RNAse H) in RT degrades the (+)ssRNA
d. End result is dsDNA

Question 15

the role of (+)ssRNA in HIV

Answer 15

just a template for RT to make dsDNA

Question 16

Understand how integration occurs, and its consequences

Answer 16

a. Integrase brings both ends of linear DNA together by binding to both at (Long terminal repeats) LTRs
b. Induces double-stranded breaks at both LTRs and the host genome
c. Ligation between viral and host genome
d. Now an integrated provirus

Question 17

what is the promoter for transcription

Answer 17

the 5’ LTR

Question 18

gene product fates

Answer 18

Half the HIV genome is produced as polyproteins that will be processed by protease AFTER RELEASE as part of viral maturation

The other gene products are expressed after splicing.

Question 19

What are retrotransposons

Answer 19

Retrotransposons = genetic regions that copy and paste themselves into different genomic locations

RNA is transcribed, RTed, then reintegrated

Parts of eukaryotic genomes from extinct viruses

Question 20

What are endogenous retroviruses

Answer 20

Endogenous retroviruses = retrotransposons that are derived from ancient retroviruses

Question 21

HIV-1 is from?

Answer 21

chimps and gorillas

Question 22

HIV-2 is from?

Answer 22

monkeys

Question 23

Which HIV has lead to the pandemic?

Answer 23

HIV-1

Question 24

What factors prevent us from getting all 40+ SIVs?

Answer 24

Exposure
1. We aren’t that exposed to non-human primates

Spillover
1. Must eat/handle bushmeat or be bit
2. Can have high viral load in blood
3. We are closely related to Old World primates (chimps)

Spread
1. Integrates into genome
2. Replicate in high amounts without killing host too fast

Question 25

Be familiar with the origins of the HIV-1 pandemic, from initial zoonotic transmission to its introduction to the United States

Answer 25

a. HIV-1 group M(ajor) came from chimps infected with SIVcpz
b. M spread in Kinshasa because it was a fast growing city due to being along the river and having railroads
c. Belgian public health campaigns fucked things up by sharing needles
d. Rail and river travel allowed mass transit
e. Introduced into NYC in the 70s

Question 26

RT inhibitor

Answer 26

prevents dsDNA intermediate formation

Question 27

protease inhibitor

Answer 27

prevents maturation

Question 28

What is the meaning behind the public health message U=U?

Answer 28

Undetectable = Untransmittable

Question 29

90-90-90

Answer 29

Inform 90% of HIV infected people of their status

Get 90% of them on ART (antiretroviral therapy)

Goal of 90% of those having suppressed viral loads

Question 30

Why do modern antiretroviral therapies require the use of a combination of drugs?

Answer 30

HIV evolves resistance quickly if only one drug

Question 31

Be familiar with how Timothy Ray Brown was cured of HIV. Why is this cure not feasible for those living with HIV?

Answer 31

a. HIV caused acute myeloid leukemia
b. Got bone marrow transplant with someone homo for CCR5(delta)32
c. BMT has 50/50 survival and is expensive and hard

Question 32

What is the latent reservoir? How is the reservoir a barrier to cure?

Answer 32

HIV goes dormant from ART and hides in cell and isn’t actively replicating

Question 33

Understand one strategy being developed for HIV cure

Answer 33

Shock and kill

Use latency reversal agents (LRAs) to wake HIV out of latency
Kill actively infected cells with immunotherapy

Question 34

What is the major hurdle in developing a preventative vaccine against HIV? What kinds of antibodies need to be elicited by a vaccine to effectively prevent HIV infection in all people globally?

Answer 34

RT cannot proofread so its very error prone and so the main antigen (Env) is extremely variable

Need broadly-neutralizing antibodies