HTLV III VIRAL PROTEINS ON B LYMPHOCYTE FUNCTION

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date9/30/866/30/89

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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