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Conditions were established and standardized for reproducibly infecting Cercopithecus with HIV-2 in the laboratory. Cercopithecus infected and vaccinated with HIV were monitored for an immune response on the basis of antigen-induced cellular proliferation and development of an antibody response detectable by Western blot assay. The anti-HIV antibody was also characterized for its ability to neutralize HIV virus. Wild Cercopithecus were tested for naturally occurring HIV infection and retroviruses isolated from five of these animals have been propagated in vitro. After screening and two cycles of plaque purification, four recombinant HIV gp120/adenovirus 2 isolates were obtained that produced HIV envelope protein as determined by immunocytochemical staining using a rabbit antibody directed against gp120. The HIV gp120 sequences in one of these were incorporated into the early region 1B rather than into the targeted early region 3. (jes)

Studies were designed to examine the molecular basis of infectivity, cytopathogenicity and genomic activation of HIV-1, with the particular emphasis on examining the factors relevant to the design of treatment and vaccine programs for combating HIV-1 infection. Three parallel approaches were followed in the course of this work. The results of this work can be summarized as follows: (1) In order to obtain a better understanding of viral gene function involved in cell killing, a series of HIV-1 viral deletion mutants were generated and the biological consequences of these mulations were examined by transfection into recipient host cells. Our results have shown that mutations in vif result in the production of morphologically normal virus particles, but which are deficient in cell-free (but not cell-to-cell) transmission to permissive cells. Mutations in the carboxy region of gp41 result in dramatic changes in the cell-to-cell transmission and cytopathic properties of the virus. (js)

Acquired immunodeficiency disease syndrome (AIDS ) was initially recognized as a separate disease in 1981. Results from research groups in France and the United States determined that a previously unknown virus called HIV is the primary aetiological agent of AIDS. Two HIV vaccines, a recombinant Adeno- HIV hybrid virus and a recombinant vaccinia HIV will be tested. The recombinant Adeo-HIV virus is being developed as part of this proposal, we will focus on whether generation and cloning of HIV specific killer T cells could be used to protect humans from 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.

Acquired immunodeficiency disease syndrome (AIDS) was initially recognized as a separate disease in 1981. Results from research groups in France and the United States determined that a previously unknown virus called HIV is the primary aetiological agent of AIDS. Two HIV vaccines, a recombinant Adeno-HIV hybrid virus and a recombinant vaccinia HIV will be tested. The recombinant Adeno-HIV virus is being developed as part of this proposal. The vaccines will be tested in two species of monkeys, chimpanzees and African green monkeys. Vaccinated animals will be challenged with a defined dose of HIV virus. Assessment of vaccine efficacy against the virus challenge will include T4/T8 ratios, Interleukin-2 production, HTLV-III serology and ability to detect infectious HTLV-III virus in peripheral blood cells. T-cell mediated immunity will be assessed by monitoring cytotoxic T cell activity and antigen-induced PBL proliferation. In Phase II of this proposal, we will focus on whether generation and cloning of HIV specific killer T cells could be used to protect humans from AIDS. Keywords: DNA recombinant, Antibody, T-cell.

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.