HIV ENVELOPE GLYCOPROTEINS AND IMMUNITY

Project: Research project

Description

Acquired immune deficiency syndrome (AIDS) is caused by infection
with the human immunodeficiency virus (HIV-1). Infection with HIV-
1 is associated with B cell hyperactivity, loss of cell mediated
immune function and frequently, defective antibody production.
This proposal is based on the hypothesis that soluble envelope
glycoproteins of HIV-1 exert significant immunological influences
and thereby contribute to the overall immune dysfunction in HIV
infection. We have previously shown that a whole viral extract of
HIV-1 influences functions of both T and B lymphocytes of normal
volunteers. Preliminary results have now shown that purified HIV-
1 envelope glycoprotein, gp160 can induce terminal differentiation
in normal B lymphocytes and gp120 can suppress normal T cell
functions in vitro. A B cell stimulatory subregion has ben
identified in the activity was found to be localized in the
carboxyl terminal of the gp41 region of the envelope. Studies proposed are aimed at identifying B cell stimulatory
epitopes of HIV-1, understanding mechanisms at the cellular and
sub-cellular level of the stimulatory and suppressive influences
of HIV proteins and lastly to identify the immunosuppressive
molecules of HIV-1. Virally mediated or modulated effects will
include study of lymphocyte activation viz. membrane potential
changes, calcium mobilization, second messengers, activation of
protein kinase C and expression of cellular genes. We propose to
test synthetic peptides spanning the B cell stimulatory subregion
to delineate the B cell stimulatory epitope of HIV-1. With these
studies, we hope to gain insight into the pathogenic mechanisms of
immune dysfunction caused by HIV-1. These studies are important
for developing a unified hypothesis incorporating the stimulatory
and inhibitory properties of HIV-1 and also have implications for
ongoing vaccine trials with HIV-1 envelope proteins and in the
development of therapeutic approaches for other immunologic
disorders.
StatusFinished
Effective start/end date3/1/894/30/03

Funding

  • National Institutes of Health: $421,448.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $389,652.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Immunity
Glycoproteins
HIV
HIV-1
T-Lymphocytes
Apoptosis
B-Lymphocytes
CD4 Antigens
Up-Regulation
Ligation
HIV Envelope Protein gp120
Cytokines
Acquired Immunodeficiency Syndrome
HIV Infections
Blood Cells
Helper-Inducer T-Lymphocytes
Vaccines
CD95 Antigens
HIV Envelope Protein gp160
Fas Ligand Protein

ASJC

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