HIV/AIDS Flashcards
What does AIDS stand for?
Acquired immunodeficiency syndrome
What kind of virus is HIV, what is it’s tropism?
virus = retrovirus
tropism = T-lymphotrophic
What are the two groups of HIV?
HIV-1 and HIV-2
What are the four subtypes of HIV-1? Briefly describe what each subtype stands for and its prevelance. Where is HIV-2 mostly found?
- group M (major)
- pandemic strain - group O (outlier)
- <10% of infections, restricted to West-Central Africa - group N (non-M. non-O)
- very rare, only in Cameroon - group P (alphabet)
- only 2 cases both in Cameroon
HIV-2 is mainly in west africa
Describe the interspecific transfer of SIV/HIV that lead to HIV-2
SIVsmm in sooty mangabey -> HIV-2 in humans
Describe the interspecific transger of SIV/HIV that lead to HIV-1 M and N
SIVcpz in chimps -> HIV-1 M and N in humans
Describe the interspecific transger of SIV/HIV that lead to HIV-1 O and P
SIVcpz in chimps -> SIVgor in gorillas -> HIV-1 P and O in humans
Describe how SIV affects monkeys
- each monkey contains its own SIV
- don’t make a significant problem in monkeys - SIVcpz is highly pathogenic to chimps
How did spillover from monekys to humans likely happen?
hunting monkeys and apes -> likely blood transfer -> infection
Where is most SIV found in wild chimps and gorillas?
chimps = Cameroon and democratic republic of Congo
gorillas = Cameroon
Describe the origin and diversification of HIV-1 M (where did it originate and where was it amplified/diversified and spread?)
originate: chimp -> human transfer = Southeast Camerooon
amplification, diversification and spread = Kinshasa
Describe how SIVcpz is deterimental to chimps, and what did this provide evidence for?
- high mortality and AIDS-like immunopathology in wild chimps infected with SIVcpz (sig difference in death rates of chimps who are infected vs healthy)
evidence = chimps get AIDS and die from it -> evidence that the interspecific jumps to chimps happened close (before) it jumped to humans
What other monkey/ape has a pathogenic SIV?
gorillas
What are restriction factors? Describe some properties of restriction factors
restriction factors = species-species barriers
properties:
- host proteins that inhibit virus replication
- expression is increased by IFN
- often antagonized by viral proteins
Name 3 human restriction factors against HIV-1, their mechanism of action, and the HIV-1 antagonist
Restriction factor: APOBEC3G
- mechanism: deamination of proviral DNA
- antagonist: vif (virion infectivity factor)
Restriction factor: Trim5a
- mechanism: premature capsid uncoating
- antagonist: capsid protein mutations
Restriction factor: tetherin
- mechanism: inhibits release of budded virion
- antagonist: vpu (Nef in many SIVs)
Describe the APOBEC3G mechanism of action, how vif antagnoizes it, and state whether it was barrier to chimp-human transmission or not.
Mechanism:
1. APOBEC3G hitchhikes into budding virions
2. deaminates cytosine -> uracil
3. impedes reverse ts
4. genome is degraded
Vif mechanism:
1. ubiquitylates A3
2. A3 is degraded
A3G was not likely a barrier because vif works well against it
Describe the Trim5a mechanism of action, how HIV antagnoizes it, and state whether it was barrier to chimp-human transmission or not.
Mechanism:
1. recognizes the capsid
2. destroys the capsid or
3. causes ubiquitylation by E3 ligase -> immune response
HIV mechanism:
1. human trim5a recognizes HIV-1 capsid poorly
Trim5a was not likely a barrier because human Trim5a does not work well against HIV-1
Describe the capsid of HIV (symmetry, and number of hexamers and pentamers)
fullurene cone: 250 hexamers and 12 pentamers
Describe the tetherin mechanism of action, how vpu/nef antagonize it, which protein does SIVcpz use, and state whether it was a barrier to chimp-human transmisson or not and why
Mechanism:
1. located on the cell surface and both ends are anchored to the p.m
2. extracellular domain allows tetherin-tetherin dimerization
3. either tethers virion to cell surface or connexts virions to each other
Vpu mechanism:
1. binds the tetherin transmemb domain
2. retains newly made tetherin to the GA
3. redirects it to lysosomes
Nef mechanism: (SIVcpz)
1. binds tetherin cytoplasmic domain
2. leads to clathrin-dependent endocytosis
Tetherin was likely a barrier to chimp-human transmisson because humans have a 5a.a del in the cytoplasmic domain of thetherin which prevents SIVcpz Nef (and Vpu) from binding tetherin
How did HIV overcome tetherin?
HIV-1 group M and N has “regained” the ability to antagonize tetherin
What is the other critical function of Vpu besides antagonizing tetherin? Which HIV-1 subtypes Vpu has this function? Which subtype has a fully functional Vpu and what is the consequence of this?
function = downregulation of surface CD4, which is required for efficient virus release
subtypes = M and O
fully functional Vpu = M -> allowed M to take off and become pandemic
Describe the long-term course of HIV-1 infection in untreated humans (describe the different phases)
Acute phase:
- large drop in the number of CD4+ T cells in the blood and GIT
- driven by the cytotoxic effects of HIV-1 and killing by anti-HIV CTLs
Asymptomatic phase:
- viral load decreases due to the immune response
- CD4+ T cell numbers in blood and GIT continue to decline
AIDS phase:
- no CD4+ T cells
- virus wins the battle
What are CD4+ T cells required for?
- optimal Ab responses
- especially class switching - activation and growth of CD8+ T cells
- activating antibacterial functions of macrophages
- maintaining lymph nose structure and function
- especially the fibroblast reticular cell network
How does early and persistent immune activation help drive progression to AIDS? Describe what causes it, what it affects, and what it leads to
caused by:
- breached intestinal barrier (from destruction of GALT) -> bacterial products (LPS) find their way into blood
- inflammatory cytokines produced by infected CD4 T cells, macrophages and DCs
affects:
- all immune cells (not just HIV-1 infected cells)
leads to:
- immune cell exhaustion (anergy)
