Considerable evidence indicates an etiological role for HTLV-III and related retroviruses in the current epidemic of AIDS. The env gene-coded proteins of retroviruses play important roles in the biological activities of these agents, and are the major targets of the protective immune response against these viruses. We have considerable experience in the characterization of the structure, functional activities, and immunological pro-erties of the env gene products of the murine leukemia viruses, which represent an excellent retrovirus model for understanding the recent human isolates such as HTLV-III. We propose to perform similar characterizations of the AIDS virus env components. Monoclonal antibodies will be prepared against the purified glycoproteins of HTLV-III and LAV. The localization and chemical nature of the epitopes on the env proteins recognized by these antibodies antibodies will be studied, and the neutralizing and cytotoxic titers of the antibodies determined, as means of identifying those sites on the env proteins which induce such activities. A binding competition assay will be developed as an efficient method of characterizing similar activities in sera of human subjects exposed to the AIDS viruses. Using appropriate antisera, the biosynthesis of the env gene products will be characterized, the contribution of carbohydrates to the maturation and function of these proteins will be determined, and the subunit organization of the env components will be elucidated. The effect of the purified HTLV-III env proteins on in vitro hematopoietic cell differentiation and functional activities will be determined. These studies should provide needed insight into the nature of these molecules which should clarify their functional roles in induction of AIDS, and which should facilitate the design of an effective vaccine against these viruses.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Virology Study Section (VR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Public Health Research Institute
United States
Zip Code
Pinter, A; Honnen, W J; Kayman, S C et al. (1998) Potent neutralization of primary HIV-1 isolates by antibodies directed against epitopes present in the V1/V2 domain of HIV-1 gp120. Vaccine 16:1803-11
Pincus, S H; Cole, R L; Watson-McKown, R et al. (1998) Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis variable lipoprotein. AIDS Res Hum Retroviruses 14:419-25
Pincus, S H; Messer, K G; Cole, R et al. (1997) Vaccine-specific antibody responses induced by HIV-1 envelope subunit vaccines. J Immunol 158:3511-20
Pinter, A; Kopelman, R; Li, Z et al. (1997) Localization of the labile disulfide bond between SU and TM of the murine leukemia virus envelope protein complex to a highly conserved CWLC motif in SU that resembles the active-site sequence of thiol-disulfide exchange enzymes. J Virol 71:8073-7
Li, Z; Pinter, A; Kayman, S C (1997) The critical N-linked glycan of murine leukemia virus envelope protein promotes both folding of the C-terminal domains of the precursor polyprotein and stability of the postcleavage envelope complex. J Virol 71:7012-9
Alsmadi, O; Herz, R; Murphy, E et al. (1997) A novel antibody-dependent cellular cytotoxicity epitope in gp120 is identified by two monoclonal antibodies isolated from a long-term survivor of human immunodeficiency virus type 1 infection. J Virol 71:925-33
Vijh-Warrier, S; Pinter, A; Honnen, W J et al. (1996) Synergistic neutralization of human immunodeficiency virus type 1 by a chimpanzee monoclonal antibody against the V2 domain of gp120 in combination with monoclonal antibodies against the V3 loop and the CD4-binding site. J Virol 70:4466-73
Demaria, S; Tilley, S A; Pinter, A et al. (1995) Bathophenanthroline disulfonate and soluble CD4 as probes for early events of HIV type 1 entry. AIDS Res Hum Retroviruses 11:127-39
Wu, Z; Kayman, S C; Honnen, W et al. (1995) Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. J Virol 69:2271-8
Warrier, S V; Pinter, A; Honnen, W J et al. (1994) A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee monoclonal antibody. J Virol 68:4636-42

Showing the most recent 10 out of 21 publications