HIV Flashcards
Retrovirus genome (proteins?)
Gag: structural proteins Pol: enzymes Env: surface protein Accessory proteins: in complex retroviruses Rev: RNA export Tat: transcativator Vif, Vpr, Vpu for pathogenesis LTRs
Retrovirus key enzyme
Reverse transcriptase.
RNA > DNA
Poor proofreading activity.
HIV replication. receptors
Receptor CD4 (Th cells), co-receptor: CCR5. Membrane fusion > viral material into cell > RT: RNA to DNA > nucleus > integrase nicks host DNA, HIV insertion into genome (lifelong infection!). DNA > mRNA > viral proteins > shuttled to membrane > budding from cell surface > maturation > infectious virion
HIV characteristics
Enveloped RNA virus.
Enzymes: RT, integrase, protease.
Infects CD4+ T cells and macrophages.
HIV immune evasion
Infects and kills Th cells.
Major target: GALT.
Sole ab target: Env. HIV is highly variable and changes epitopes in response to pressure from neutralizing ab
Env immune evasion
Glycans on Env protect underlying epitopes from recognition by ab. Variable domains are displayed at Env surface. Conserved domains which would be good targets for ab are either hidden inside Env or are only shortly exposed during entry.
HIV therapy targets
Inhibitors target viral enzymes (integrase, RT, protease).
Three inhibitors have to be combined!
Salvage therapy: entry inhibitors
Does therapy cure HIV?
Maintenance in latent reservoirs (long-lived cells) prevents eradication of virus > no cure!
HIV origin
Originated from Simian immunodeficiency viruses (SIV).
Zoonotic transmission.
HIV1: SIV-cpz from chimpanzees
HIV2: SIV-sm from sooty mangebey
Consumption of primates for food played an important role.
HIV-1 vs -2 vs SIV
1: responsible for AIDS pandemic (group M!), causes AIDS in 97.5% of infected.
2: endemic in West Africa/India, less pathogenic, causes AIDS in 25%
SIV: present in African primates, usually do not cause disease despite high levels of viral replication, experimental infection of Asian macaques induces AIDS, important animal model
Recognition of and innate defense against viruses
TLRs recognize PAMPS:
RIG1 and MDA5 recognize viral RNA,
IFI16 and cGAS recognize viral DNA.
PAMP recognition induces IFN production:
IFN binding to IFN receptors induce expression of ISGs in a JAK/STAT dependent fashion.
ISGs that inhibit HIV: restriction factors
ISG
Interferon stimulated genes.
Induced by IFN (viruses: type I, III) via JAK/STAT. Facilitate antiviral state.
Viruses are sensed by..
TLRs (recognize PAMPs)
RIG-I-like receptors (cytoplasmic RNA sensors: RIG-I, MDA5)
DNA sensors (cGAS)
HIV sensors
Sensed in cytoplasm by cGAS and IFI16.
Sensed in endosome by TLR7.
ISG that inhibit HIV
Restriction factor (IFN inducible, cell autonomous, under positive selection, frequently inhibited by viral accessory proteins)
