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Molecular Aspects

A Summary of "AIDS and the Immune System"

Human Immunodeficiency Virus (HIV) demands particular attention as it currently afflicts over 5 million people who will undoubtedly contract AIDS and the AIDS-related illnesses. With the rate of infection climbing and little understanding that would offer a hope of a vaccine or cure, global resources should be allocated to the study of this virus.

HIV consists of a lipid bilayer with glycoproteins gp120 and gp41. Further inside the layer, there is a p17 protein, 2 strands of viral RNA, reverse transcriptase, protease, ribonuclease, and integrase. The glycoproteins easily bind to cell receptors (CD4) on helper T cells (T4).

With the introduction of HIV, the virus quickly infects T4 cells. However, because of the similarities of the gp120 protein to glycoproteins on healthy cells, some normal T4's may attack other healthy T4 cells, may stop dividing, or commit cellular suicide (apoptosis). The fast infection causes flu symptoms and begins to infect and congregate in the lymph nodes causing localized swelling. HIV will eventually lower the lymphocyte count in the bloodstream.

Upon infecting a cell, HIV converts its 9,200 base pair RNA to DNA using a sloppy reverse transcriptase which causes errors in 1 out of every 2,000 base pairs. Some drugs, azido thymidine (AZT), dideoxycytidine (ddC) and didoxyinosine (ddI) plug up the reverse transcriptase. The newly synthesized viral DNA is integrated into the chromosomes of the host cell by integrase. Current research is attempting to block this step and thus cause HIV to decay in the cytoplasm without causing further harm. Once integrated into the chromosomes, HIV faces the NF-B/Rel proteins which block transcription. HIV first produces a 2,000 base pair RNA which codes for a promoter (tat) that will encourage further transcription of the HIV genome by binding to the TAR sequence. There is another protein, nef which has an unknown function. The rev protein concatenates the viral RNA together and transports it to the cytoplasm.

Immune response increases with exposure to the HIV protein-lipid shell. Gene therapy techniques to transfer known resistance genes to humans face feasibility problems as does any other solution. Although education has show lackluster progress, it is the only option currently feasible and available.

Bibliography

Greene, Warner C. "AIDS and the Immune System." Scientific American. Sept. 1993. p99-105.