Disseminating RNA Viruses II

Question 1

NRTIs

Answer 1

Nucleoside reverse transcriptase inhibitors

Mimick the enzyme’s natural nucleoside substrates, but lack the 3’ hydroxyl for continuation of the chain.

Question 2

Interactions between HIV and the CD4 T cell membrane

Answer 2

1. HIV gp120 recognizes CD4 and brings itself into CD4 proximity.
2. HIV gp120, while remaining bound to CD4, binds to CCR5 or CXCR4.
3. HIV gp41 uses these two anchors to pull itself close to the cell membrane and fuse its envelope with the cell membrane.

Question 3

ISTIs

Answer 3

Integrase strand-transfer-inhibitors

Highly potent and have favorable pharmacokinetics. Well tolerated because there is no overlap with native host biochemistry.

Question 4

Azidothymidine

Answer 4

NTRI that mimicks Adenosine

Question 5

Contribution of latency to HIV pathogenicity

Answer 5

HIV’s provirus may remain latent within memory T cell genomes for years, where it is inaccessible to antiretroviral therapies.

This makes HIV a chronic condition if a sufficient number of memory T cells have been altered by insertion of a provirus.

Question 6

Fidelity of the HIV reverse transcriptase

Answer 6

Not great. On average, 1 mistake is made per copying of the HIV genome (~10 kbp).

This contributes to HIV mutagenicity and makes it difficult for antibodies to target.

Question 7

The conserved regions of gp120 are. . .

Answer 7

. . .sequestered behind nonconserved regions that are poor antibody targets.

Question 8

How does HIV take advantage of host machinery to produce multiple gene products per gene?

Answer 8

The virus employs differential mRNA splicing, ribosomal frameshifting and polyprotein cleavage in order to achieve this effect.

Question 9

“U=U” Rule in microbiology

Answer 9

Undetectable = Untransmissible

Not universal, but it at least applies to HIV

Question 10

Ultimate fate of infected CD4 T cells

Answer 10

Lysis upon HIV budding

Question 11

Enfurvirtide

Answer 11

Analog of the gp120 fusion peptide which binds to gp41 and blocks a conformational change required for fusion of the HIV and host cell membranes.

Question 12

Gag

Answer 12

Encodes the capsid protein

Question 13

Answer 13

Kaposi’s Sarcoma

Occurs almost exclusively in immunocompromised patients

Question 14

Integrase

Answer 14

Mediates the insertion of reverse-transcribed proviral DNA into a host cell genome.

Question 15

Why does HIV preferentially target activated T cells?

Answer 15

Because this is where CCR5 and CXCR4 are expressed at high levels.

Question 16

HIV protease

Answer 16

Cleaves an HIV polyprotein precursor into its individual, functional protein products. If this cleavage does not happen, these functional proteins will not be produced.

Question 17

Ritonavir

Answer 17

HIV protease inhibitor

Requires “boosting” (administration with a secondary drug which acts ot increase serum levels of the primary drug by inhibiting hepatic drug metabolism of the primary drug)

Question 18

Resistance of HIV often develops to ____.

Answer 18

Resistance of HIV often develops to reverse-transcriptase inhibitors and HIV protease inhibitors.

Question 19

Common opportunistic infections affecting AIDS patients

Answer 19

Question 20

HIV structure

Answer 20

Question 21

Maraviroc

Answer 21

blocks association of the CD4-bound virion with the CCR5 co-receptor required to trigger membrane fusion and virion entry.

A “last resort” antiretroviral used when extensive resistance to other antiretrovirals leaves options limited.

Question 22

Ritonavir-HIV Protease Crystal Structure

Answer 22

Question 23

Human immunodeficiency virus

Answer 23

Belong to a family of simian immunodeficiency viruses. Retroviridae. Enveloped, non-segmented +dsRNA.

Integrates a provirus into the genome of infected cells.

Question 24

Certain alleles of the ____ gene render small European populations highly resistant to HIV infection.

Answer 24

Certain alleles of the CCR5 gene render small European populations highly resistant to HIV infection.

Question 25

“Elite controllers”

Answer 25

HIV patients whose immune systems somehow manage to reign in the HIV infection and remain healthy despite chronic infection.

Currently the target of intense research.

Question 26

Broadly-Neutralizing Monoclonal Antibody

Answer 26

In clinical trials. Anti-HIV serum.

Question 27

NNRTIs

Answer 27

Non-nucleoside reverse transcriptase inhibitors

Viral resistance to these drugs arises through mutations at or around this cleft, and are in general highly cross-resistant among members of this class

Question 28

HIV life cycle

Answer 28

Question 29

Only ____ and ____, of RNA viruses, may integrate into the host genome

Answer 29

Only orthomyxoviruses and retroviruses, of RNA viruses, may integrate into the host genome

Question 30

Kaposi’s sarcoma is caused by. . .

Answer 30

HPV8

Question 31

HIV infetion diagram

Answer 31

Question 32

Chronology of HIV diagram

Answer 32

Question 33

Antigenic “shift” vs Antigenic “drift”

Answer 33