HIV Flashcards
What’s the difference between HIV-1 and HIV-2?
HIV-1 subgroups
M,N O - derived from different subspecies of chimpanzee
Why have the subtypes of M broken down?
Coinfection and RT template switching
Where does recombination often occur?
Occurs between copackaged dimeric viral RNA genomes
HIV genome
gag, pol, env, tat, rev, vif, vpr, vpu, nef
HIV receptor targets
CD4 + CCR5 in immune cells
Viremia
HIV acute infection
Virus replicating in cells
Immune response clears virus from blood
Clinical latency - battle between immune system + viral replication
Development of AIDS
HIV starts killing off CD4 cells - not enough left in immune system
= AIDS
Stages of HIV infection
Primary infection
Acute HIV infection
Clinical latency
Onset + opportunistic infections
Death
HIV steady state
- The amount of HIV in the body reaches a relatively stable level, usually several months after infection.
- The virus has established a balance with the immune system, and the rate of viral replication is roughly equal to the rate at which the immune system is able to control the virus.
- During the HIV steady state, the number of CD4 T-cells, also stabilizes.
Host immune defences to HIV
- Interferons
- Neutralising antibodies
- Trim5alpha
- APOBEC3G
- Tetherin
- CCR5 deletion
Interferon defence against HIV
Type 1 interferons produced in infected and uninfected
Induce antiviral state in uninfected cells
e.g. Translation inhibitory protein produced
TIP
translation inhibitory protein
makes ribosomes check for caps
Neutralising antibodies
Producedusing HIV p24 antigen
Neutralising antibodies
Producedusing HIV p24 antigen
TRIM5alpha
Retrovirus restriction factor
Innate immune defense in cells
Recognizes motifs within viral capsid proteins, which causes the TRIM5α to smother the (not yet uncoated) capsid in a reticulatory way so as to form a repeating regular hexagonal net, two sides of each hexagon being made up of two spokes of a three-way hub and spoke trimer
APOBEC3G
Cytidine deaminase
Edits C to U in viral negative strand
GA hypermutation of viral positive strand
Vif tags APOBEC for degradation
Tetherin
Induced by interferons
Prevents release of HIV
Vpu binds to tetherin and targets it for degradation
CCR5 deletion
Deletion in receptor prevents HIV-1 infection = NATURAL IMMUNITY
Combination therapy
Treatment that uses a combination of three or more drugs to treat HIV infection
Prevent drug resistant mutants
