Retroviruses II Flashcards
What caused the major decline of AIDS-related deaths in 1995?
Advent of protease inhibitors and HAART.
By what routes can HIV be transmitted?
Blood inoculation (needles, transfusion)
Sexual contact (vaginal or anal, not really oral)
Perinatally (intauterine, birth, via breastmilk)
Close personal contact
Describe the additional factors encoded by HIV’s “complex” genome.
Tat - Activates transcription.
Rev - Tranlocates mRNA from nucleus.
Vif - Degrades a host deaminase.
Vpu - Inhibits Tetherin.
What cells are targeted by HIV?
Mainly CD4+ T-helper cells, but also dendritic cells and macrophages (former carries virus at surface, latter can be infected but not killed).
Microglia in the CNS can also be targeted.
What cells are targeted by “M-tropic” virions?
What is the surface co-receptor responsible?
Primary T-cells and macrophages.
CCR5.
What cells are targeted by “T-tropic” virions?
What is the surface co-receptor responsible?
Primary T-cells and T-cell lines.
CXCR4.
What is the consequence of a Δ32 deletion in the CCR5 gene?
Can a drug mimic this effect?
The result is a mutant CCR5 which is not recognized well by env.
Maraviroc is an antagonist of CCR5.
What HIV protein facilitates “snapback” fusion?
What HIV protein specifies M/T tropism?
gp41 (originally from gp160/env)
gp120 AND gp41 seem to be involved.
Describe the fusion process for an HIV virion. Can this be blocked?
gp120 recognizes CD4, and changes conformation to expose the co-receptor binding site. gp41 also binds and changes conformation in such a way as to pull the two membranes together.
T-20 (Fuzeon) blocks the snapback by binding gp41’s N-terminus.
What role do the lymphatics play in HIV infection?
Lymph nodes are the initial site of virus spillover into circulation (viremia).
Following the acute infection, the lymph nodes remain sites of replication for HIV.
How does HIV kill CD4+ cells?
Lysis due to virion production, induction of apoptosis, formation of “syncytia” due to env left in the plasma membrane.
There is also indirect killing due to immune system (CTLs). Soluble gp120 may cause targeting of healthy cells for death.
What happens during acute and latent HIV infection?
In acute infection, there is a strong immune response and an initial clearing of the virus. In the latent stage, the virus remains in the lymphatics and continues to degrade CD4+ cells in the face of a strong immune response.
What lab tests exist to monitor HIV viral load?
Serologies: Ab ELISA (fast and cheap), Ag ELISA (early-detection), Western blot (to confirm Ab ELISA).
RNA RT-PCR
Real time RT-PCR
Name 5 possible therapeutic targets in HIV treatment.
- Reverse transcriptase
- Integrase
- Protease
- Fusion
- “Entry” (co-receptor)
What is HAART?
Highly Active AntiRetroviral Therapy. Consists of a triple therapy of antivirals. Most of these combinations include a reverse transcriptase inhibitor.
