Molecular Mechanisms of Cytopathogenicity of Primate Lymphotropic Retroviruses: Relevance to Treatment and Vaccine for AIDS.

The molecular basis of infectivity, cytopathogenicity and genomic activation of Human Immunodeficiency Virus Type 1(HIV-1) was investigated by generating deletion mutations in sor, 3'orf, 5' region, and LTR. These studies show that the sor gene is crucial for the generation of infectious virus. Analysis of 3'orf indicate that deletions in the amino terminus (which overlaps the carboxy terminus of gp41) result in significant reduction in viral propagation. Studies with the LTR sequency have delineated an enhancer activity, an sp-1 bending site, and a tat response region (TAR). Genomic clones containing the integrated provirus of Simian T-Cell Lymphotorpic Virus Type III(African Green Monkey) (STLV-II(AGM)) and HIV-2(NIH-Z) have been isolated. Their nucleic acid sequence has been determined and subjected to computer analysis. A Comparison of the nucleotide sequences of these two new viral isolates with HIV-1 indicates that these new retroviruses are structurally similar to HIV-1 and belong to the same class of viruses as HIV-1. STLV-III and HIV-2(NIH-Z) exhibit a greater homology among themselves than with HIV-1. A study of biologically active forms of these viruses will aid in understanding why these new viruses are non-pathogenic. Keywords: Vaccines, Acquired immune deficiency syndrome, Virus diseases, Immunosuppression, Deoxyribonucleic acids.