HIV Flashcards
What is the function of HIV Rev protein?
It stabilised and transports unspliced and partially spliced RRE+ HIV RNA to the cytoplasm
What does Vif protein do?
Degrades APOBEC3
What does Pneuocystis jirovecii cause?
Pneumonia
What does TRIM5a do?
A endogenous human protein that destabilises the viral capsid
What viral protein is required for reactivation of transcription after a peroid of latency?
Tat
Apart from depleting T cells, what other effects does HIV infection have on the immune system in general?
Reduces neutrophil killing of bacteria
Increase B cell production of antibodies, including autoantibodies
Decrease macrophage phagocytosis, chemotaxis and killing
Decreases NK function
Which does HIV preferentially bind to early in infection, CCR5 or CXCR4?
CCR5
Why has vaccine development been so difficult?
Because envelope gp120 is highly variable
Which nucleoside is acyclovir an analogue of?
Guanosine
Is T cell depletion only caused by direct destruction of infected cells?
No, indirect destruction of uninfected cells also occurs.
eg Via incorporation of uninfected cells into syncitia
What adverse consequences of infection are seen despite viral control with HAART?
HIV-associated metabolic syndrome
Excess pathogens
Loss of Tregs
Microbial translocation through gut
CVS disease
Liver disease
How is it possible for HIV RNA production to occur in patients on HAART?
Latency in CD4+ T cells - particularly memory T cells
Replication in sanctuaries away from HAART therapy ie Brain, testis and gut
Replication in immunologically privileged sites
What type of virus is HIV?
Lentivirus
Icosahedral capside
Enveloped
+ssRNA
What is ribavirin?
A guanosine analogue that can target multiple viruses
What is the name of the viral protein that drives membrane fusion?
gp41
What does the HIV provirus’ promoter respond to?
Viral Tat protein
NFcappaB - a transcription factor involved in T cell activation
At mutation in delta32 CCR5 confers what for the human?
Homozygous confers resistant
Heterozygous confers slowed disease progression
Which has phosphate groups, nucleosides or nucleotides?
Nucleotides
What does the gag gene encode for?
Matrix
Capsid
Nucleocapsid
What long does primary HIV last?
1-4 weeks
What does APOBEC3G do?
It is an endogenous human protein that induces lethal hyper-mutations
What are some strategies HIV uses to block the expression of MHC-1?
Lysosomal degradation of MHC-1 by Nef and Vpu
Directing MHC-1 into the proteosome by Vpu
Tat inhibiting MHC-1 gene transcription
What causes chronic immune-activation? What is the consequence of it?
Lost of gut mucosal barrier > microbial products leak into systemic circulation > PAMPs stimulate immune cells > pro-inflammatory cytokines are elevated
- CD4+ T-cells enter cell-cycle and die
- CD8+ T cells become trapped in lymph nodes
- B-cells make auto-Ab
Why must you use 3 drugs in a combination therapy?
The chance of spontaneous viral mutation to evade 3 antivirals is highly improbable
Is decline in CD4 cells faster or slower with hepatitis G co-infection?
Slower
What is required for maturation of the viral particular after budding?
Activity of viral protease
What is the incubation period of primary HIV infection?
2-4 weeks
Why don’t most antibodies to the HIV env neutralise the virus?
It is highly glycosylated
Why does acyclovir only target viral DNA replication?
Because it requires viral thymidine kinase to add the first phosphate group
What is the presentation of primary HIV infection?
Flu-like illness
- Fever
- Myalgia/arthralgia
- Nausea/vomiting/diarrhoea
- Weight loss
What is Kaposi’s sarcoma caused by?
Infection by human herpesvirus 8
What does HAART stand for?
Highly active anti-retroviral therapy
How does Raltegravir work?
Inhibits integrase to block strand transfer
Where is the sequence variation highest in the HIV-1 genome?
In the env V region
How often to nucleotide changes occur to transcription of DNA from RNA?
Once per genome replication
How is viral fusion/entry inhibited by antivirals?
Coreceptor antagonists
- For CCR5 = Maraviroc
- For CXC4 = AMD-11070
Preventing unfolding
- Enfuvirtide
How do the protease inhibitors of HIV maturation work?
They have analogous regions that maturation enzyme will bind to instead of the viral target
What does Vpu do?
Facilitates the release of fully infectious virions and counteracts innate immunity factors (degrades CD4, antagonizes tetherin, inhibits surface expression of CD1d)
Describes HIV’s structure in terms of its layers
Outer bilipid membrane
Matrix protein beneath, complexing with the envelope
Capsid
Nucleocapsid contain the RNA genome
What percentage of T-cells are lost within primary HIV-1 infection?
>60% of mucosal T-cells
What do nucleoside analogues lack that prevents them from being added to the growing DNA chain by polymerase?
3’ OH
Via what mechanism does HIV get from a local infection into the blood?
Virus infection dendritic cells > these fuse with CD4+ T cells > both travel to regional lymph nodes > HIV is spread to activated CD4 T cells > those infected cells enter the bloodstream
What is the of the coreceptors that HIV binds to after initially binding to CD4?
CCR5
CXCR4
Which can be detected first, HIV antigen or anti-HIV antibody?
HIV p24 Antigen
Which strain of HIV-1 is transmitted between people?
R5
What does tetherin do?
It is a endogenous human protein that inhibits virus release
Which protein is required for the maturation of HIV particles?
Gag-Pol precursor protein
What structural property do all nucleoside reverse transcriptase inhibitors share?
They lack the 3’ OH
What is the limitation of targeting coreceptors with antagonists?
The other coreceptor is selected for
Why is the function of the long terminal repeat?
Acts as the HIV gene promoter once the provirus have been integrated into the host genome
What viral ligand binds CD4 of T cells and macrophages?
gp120
Which coreceptor is associated with greater pathogenicity?
CXCR4
Epidemiologically, how does the distribution of HIV infection differ in Australia compared to the rest of the world?
In Australia homosexual male are predominantly affected while in worldwide it is predominantly heterosexual women
Where does reverse transcription occur?
Within the viral capsid when it is in the cytoplasm of the infected cell
How is the long terminal repeat created?
Duplication of the end of the viral RNA sequence
In general, how do non-nucleoside reverse transcriptase inhibitors work?
Directly inhibit the reverse transcriptase enzymes by some mechanism
