HIV Flashcards
Self Genes that inhibit HIV propogation
- TRIM5a ○ Destabilisation of viral capsid - APOBEC3G ○ Lethal hyper-mutations - Thethrin ○ Inhibition of virus release
Proteins that inhibit MCHI on surface of CD4 cells
Three genes tat, vpu and Nef will prevent the expression of MHCI on the surface of Tcells. Tat inhibits MHCI transcription, Vpu will direct MHCI to the proteosome and nef and vpu will promote MHCI to the lysosome.
Three functions of Vpu
- Degarde CD4
- Antagoniised tethrin
- Inhibits surface expression of CD1d (lipid antigens to T cells from DCs)
What does APOBEC3G do and what HIV protein degrades it
Will introduce G-A lethal hypermutations into the ssDNA genome of HIV. Vif protein will degrade it
What are the three phases of HIV infection
Primary, asymptomatic and then symptomatic
Initial infection progression of the HIV
Transmission to DCs, which will then transport to lymph nodes and expose to CD4+. Now the virus in HIV will replicate in CD4+ cells and will disseminate in the blood to seed other lymph nodes to maintain a position/location for their latency stage. in this stage CD4+ cells will deplet for around 6-9 weeks before returning to higher levels by 12 weeks
What are the mechanisms by which we can test for HIV
RT-PCR for the RNA of HIV by around 20 days, from 24 days we can test for proteins via ELISA nd we can detect a HIV antibody by 40 days
What are the mechanims by which HI escapes immune evasion
They have a very error prone Reverse Transcriptase and hence 1:10,000 NT are not inserted correctly and hence there is a large probability of postive mutations arising, this leads to change in antigen targets on envelope proteins such as gp120
What are the features of the asymptmatic phase
lasts for around 6 years in which the CD4+ population will decline. When the CD4+ count reaches lower than 200/ul
Symptoms of Primary phase
Will typically present with fever, myalgia, nausea and vomiting, weightloss and lymphadenopathy with transient CD4+ depletion
What are the mechanisms by which CD4+ cells decline
§ Indirect
□ Cytolysis of infected CD4+ cells by CD8+ cells
□ Incoproation into giant multiinucleated cells
□ Immune activation of CD4+ cells leading to death
§ Direct
□ Direct destruction of the infected cells
WHat is the affect of HIV on B cells
They increase their antibody secretion but they are typically auto-antibodies
What are some of the AIDS defining illnesses
□ Karposi's Sarcome (Herpes virus 8) □ Cryptococcus □ Histoplasma □ TB □ Pneumocystis carnii/jerovicii pneumonia □ Mycosis □ CMV □ M avium complex □ Candida Albicans (Severe head infections) □ Lymphomas
What are some viral factors that determine virulence
○ Attenuated strain
○ R5 or X4 phenotype
○ Co-oinfection with HepG
What are some host factors that determine virulence
○ CCR5 delta 32 mutation ○ CCR5 promoter region ○ HLA type § B 13,27,51 and 57 ○ Immunology § Grade of immune response Age
