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HIV-1Provirus



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Organization of HIV 1Provirus Size 9kb Contains 9 genes encoding 15 proteins 1 Early events of HIV infection Membrane Receptor Complex Viral core Binding of envelope gp120 prompts p41 to project 3 fusion domains that harpoon the membrane resulting in fusion HIV Integration leads to either latent or transcriptionally active infection 2 1 Host Response to HIV 1 infection First Phase CD8 T cell response of immune system controls initial destruction of memory effector CD4 T cells but does not eliminate infectious virus primarily located in monocytes and memory CD4 T cells Antibodies to HIV 1 are formed but these neither clear the infection nor are protective Acute illness flu like Clinical asymptomatic phase 2 12 or more years Second Phase HIV 1 escapes the CD8 T cell response and mutations in the viral envelope now favor infection and destruction of na ve CD4 T cells Acquired immune deficiency AIDS appears upon depletion of critical CD4 T cell subsets 3 Immune response to HIV 1 and effects of HIV infection CD4 T cells l CLINICAL Flu like Illness Asymptomatic phase AIDS Chronic lymphadenopathy HIV Symptomatic phase Mucous membrane Infections etc 4 2 Host Parasite Relationships of HIV Reverse transcriptase has no proofreading function and creates a vast number of mutations HIV must adapt and evolve in an environment determined by attributes of the host s immune system MHC alleles TCR repertoire Polymorphism of viral entry receptors Chemokine and cytokine milieu e g parasitic infections Other genes regulating immune response Prior immune history Age Outcome of infection depends on biology of host especially whether immune response targets critical 5 HIV structures and HIV 1 mutational capacity etc HIV 1 genomically highly diverse reflecting MHC selection HIV 1 Phylogenetic relationships HIV 2 6 HIV 3 Cellular Specificity Tropism of HIV strains Based on envelope structure The viral envelope contains sequences that interact with a membrane viral receptor complex composed of



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