Disseminating RNA Viruses II Flashcards
NRTIs
Nucleoside reverse transcriptase inhibitors
Mimick the enzyme’s natural nucleoside substrates, but lack the 3’ hydroxyl for continuation of the chain.
Interactions between HIV and the CD4 T cell membrane
- HIV gp120 recognizes CD4 and brings itself into CD4 proximity.
- HIV gp120, while remaining bound to CD4, binds to CCR5 or CXCR4.
- HIV gp41 uses these two anchors to pull itself close to the cell membrane and fuse its envelope with the cell membrane.
ISTIs
Integrase strand-transfer-inhibitors
Highly potent and have favorable pharmacokinetics. Well tolerated because there is no overlap with native host biochemistry.

Azidothymidine
NTRI that mimicks Adenosine

Contribution of latency to HIV pathogenicity
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.
Fidelity of the HIV reverse transcriptase
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.
The conserved regions of gp120 are. . .
. . .sequestered behind nonconserved regions that are poor antibody targets.
How does HIV take advantage of host machinery to produce multiple gene products per gene?
The virus employs differential mRNA splicing, ribosomal frameshifting and polyprotein cleavage in order to achieve this effect.
“U=U” Rule in microbiology
Undetectable = Untransmissible
Not universal, but it at least applies to HIV
Ultimate fate of infected CD4 T cells
Lysis upon HIV budding
Enfurvirtide
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.
Gag
Encodes the capsid protein

Kaposi’s Sarcoma
Occurs almost exclusively in immunocompromised patients
Integrase
Mediates the insertion of reverse-transcribed proviral DNA into a host cell genome.
Why does HIV preferentially target activated T cells?
Because this is where CCR5 and CXCR4 are expressed at high levels.
HIV protease
Cleaves an HIV polyprotein precursor into its individual, functional protein products. If this cleavage does not happen, these functional proteins will not be produced.
Ritonavir
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)
Resistance of HIV often develops to ____.
Resistance of HIV often develops to reverse-transcriptase inhibitors and HIV protease inhibitors.
Common opportunistic infections affecting AIDS patients

HIV structure

Maraviroc
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.
Ritonavir-HIV Protease Crystal Structure

Human immunodeficiency virus
Belong to a family of simian immunodeficiency viruses. Retroviridae. Enveloped, non-segmented +dsRNA.
Integrates a provirus into the genome of infected cells.
Certain alleles of the ____ gene render small European populations highly resistant to HIV infection.
Certain alleles of the CCR5 gene render small European populations highly resistant to HIV infection.
“Elite controllers”
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.
Broadly-Neutralizing Monoclonal Antibody
In clinical trials. Anti-HIV serum.
NNRTIs
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
HIV life cycle

Only ____ and ____, of RNA viruses, may integrate into the host genome
Only orthomyxoviruses and retroviruses, of RNA viruses, may integrate into the host genome
Kaposi’s sarcoma is caused by. . .
HPV8
HIV infetion diagram

Chronology of HIV diagram

Antigenic “shift” vs Antigenic “drift”
