hiv/aids

• HIV-1 Central africa, europe, usa
• HIV-2 West africa: longer latency, slower, les severe progression

HIV binds to CD4 receptor and one of 2 co-receptors on the surface of a CD4+ T- lymphocyte. It then fuses with the host cell, and releases RNA into it.

• Step 2
• HIV enzyme called reverse transcriptase converts the single-stranded HIV RNA to double-stranded HIV DNA

• Step 3
• The newly form HIV DNA enters host cells nucleus where HIV enzyme called Integrase "hides" the HIV DNA within the host cell's own DNA. The integrated HIV DNA is called provirus. It may remain inactive for several years producing few or no new copies of HIV.

• Step 4
• The host cell receives a signal to become active. The provirus uses RNA polymerase to create copies of the HIV genomic material as well as sorter strands of RNA called messenger RNA (blueprint to make long chains of HIV proteins)

• Step 5
• HIV enzyme protease cuts the long chains of HIV proteins into smaller individual proteins. a new virus particle is assembled

• Step 6
• the newly assemble virus pushes out from host cell. it steals part of the cells outer envelope. This envelope is studded with protein/sugar combination. HIV glycoproteins are necessary for the virus to bind CD4 and coreceptors. The new copies of HIV can now move on to infect other cells

• 1: infection: infects, and impairs function of Tcell bound macrophages and Thelper cells, suffer flulike symptoms due to burst of virus before immune response (2-6 weeks)
• 2: latency: Viral replication largely in lymp nodes
• 3: rapid virus production: drop in CD4 Tcell count to <400
• 4:Continued low CD4 T cell count: T cells become less functional
• 5: CD4 T cell <200: viral/fungal infections of skin and mucous membranes
• 6: AIDs: CD4 count <100, oppurtunisitic infections, visrus production and Cd4 cell turnover are rapid (billion viruses/day)

• Proozoal/parasitic: pneumonia
• Fungal: candidiasis
• Bacterial: salmonella myobacteriosis TB Clostridium
• Viral: herpes, cytomegalovirus
• Neoplasms: kaposi sarcoma, non hodgkin lymphoma, lymphoma of brain, cancer of uterine cervix
• Aids encephalopathy (dementia), Nephropathy, Retinopathy (100%)

• AIDS DEMENTIA
• Infection of microglia (interstitial cells of CNS) and macrophages: does not infect neurons, may initiate a mechanism for neuronal cell death
• Associated with poor prognosis
• Before drug cocktail 20-30% developed Aids related dementia now 10%

• Highly active antiretroviral therapy (HAART)
• Inhibit ability of HIV to make a DNA copy: non nucleoside reverse transcriptase inhibitors NNRTIs, Nucloside/nucleotide reverse transcriptase inhibitors NRTIs
• Interfere with enzyme protease activity: protease inhibitors PIs
• Interfere with HIV CD4 receptor site binding and entry into cells: Fusion inhibitors
• Integrase inhibitors

• Antibodies not effectiv
• reverse transcription sloppy
• multiple strains
• high viral turnover
• 30-40 mutation variations/rate per person
• JULY 2010: 2 powerful antibodies that neutralize 91% of HIV strains in the blood of an HIV infected person