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

The molecular basis of virus transmission, cytopathogenicity, viral particle formation and genomic activation of HIV-1 was investigated through the use of deletion mutants in the vif, nef, 5' region and LTR. The Biological effects of these alterations were examined following transfection into a variety of cell lines. Mutants with deletions of 37 amino acids at the 3' end of gp41 are capable of producing infectious virus particles and of transmitting virus to H9 cells. The last 6 amino residues of gp41 appear to be important in cell killing, while the last 17 amino acid residues appear to be important for cell to cell transmission. The cytopathic effect of the C-terminal gp41 deletion mutants equaled that of the wild-type virus. Therefore, these studies suggest that caution should be used in selecting candidate immunogens for vaccination derived from the HIV env region. Keywords: AZT; Aids; HIV; HIV-1; Lymphotropic viruses, Cytopathogenicity, RA I, DNA sequence, Gene function, Transactivation.