The etiologic agent for the acquired immunodeficiency syndrome (AIDS) is now firmly established to be the retrovirus termed as the human T lymphotropic virus, HTLV III. The disease is characterized by a marked polyclonal B cell activation, a profound and progressive loss of immunity and depletion of the T4 subset of lymphocytes. Paradoxically, the best molecular biological techniques have shown that only very few cells in peripheral blood are productively infected with this virus. In this proposal, the hypothesis being forwarded is that non-viable constituents may be responsible, at least in part, for the profound immunologic abnormalities that occur in AIDS. Preliminary experiments have revealed that exposure of peripheral blood lymphocytes to a relatively low concentration of a preparation made from disrupted, band-purified viral concentrate results in increased immunoglobulin secretion by the B lymphocytes, and at the same dosages, the preparation is inhibitory for in-vitro immunoglobulin synthesis when B cells are stimulated with other known polyclonal B cell activators, pokeweed mitogen, Staphylococcus aureus and Epstein Barr virus. We plan to test this hypothesis further, by a) determining the cellular mechanisms by which the observed stimulation and inhibition of B lymphocyte function is effected, b) analysing the production of HTLV III specific antibody in lymphocyte cultures and c) identifying, in molecular terms the individual protein(s) of the HTLV III virus responsible for these effects. The indicator systems consist of well-established assays for non-specific and antigen-specific antibody production by lymphocytes. Cells from healthy individuals and from patients with AIDS will be tested. Such studies should greatly enhance our understanding of the mechanism of immunologic dysfunction occurring in AIDS and may contribute to the development of therapeutic approaches to AIDS and other diseases.
| Chirmule, N; Kalyanaraman, V S; Saxinger, C et al. (1990) Localization of B-cell stimulatory activity of HIV-1 to the carboxyl terminus of gp41. AIDS Res Hum Retroviruses 6:299-305 |
| Chirmule, N; Kalyanaraman, V S; Oyaizu, N et al. (1990) Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. Blood 75:152-9 |
| Chirmule, N; Saxinger, C; Pahwa, S (1989) Influences of related retroviruses on lymphocyte functions. FEMS Microbiol Immunol 1:271-8 |
