IN VIVO IMMUNE ACTIVATION/ FIV GENE EXPRESSION

Project: Research project

Project Details

Description

A long latent phase of HIV-infection, signified by an asymptomatic state,
exists between initial infection and clinically detectable, immunologic
abnormalities and manifestations of the disease in HIV-infected
individuals. In vitro observations suggest that stimulation of mononuclear
cells with mitogens or antigens may enhance HIV expression and accelerate
disease in vivo. The immune stimulation can result from exposure to simple
protein antigens or from more complex immunologic stimuli induced by
incidental infectious diseases. The main objective of the present proposal
is to examine the role of mitogens, antigens, and incidental infections in
inducing or enhancing HIV gene expression in vivo by using feline
immunodeficiency virus (FIV)-infected cats as a small animal model for
human AIDS. Molecular and immunohistochemical methods will be applied to
localize and quantitate viral gene expression (DNA, RNA, protein) at tissue
and individual cell level in vivo. Development of the disease will be
followed clinically and pathologically. Regional and systemic effect of immune activation due to mitogens and
antigens on FIV gene expression and disease progression will be determined.
T-cell specific (concavalinA), T- and B-cell specific (poke weed mitogen)
and B-cell specific (Nocardia-delipidated cell mitogen) mitogens will be
used to investigate how T- and B-cell activation in vivo will influence FIV
expression. For antigenic stimulus, we will use two forms of a synthetic
polypeptide antigen, multi-copoly(Phe-Glu)-poly(Pro)-poly(Lys), one
containing D-amino acids and the other, containing L-amino acids. The D-
form induces thymus independent antibody response, whereas, L-form induces
T-dependent response. If mitogenic or antigenic stimuli do upregulate FIV
expression, an attempt will be made to block immune activation by systemic
cyclosporinA treatment and examine FIV gene expression. To determine the effect of other microbial infections on FIV gene
expression, FIV-infected cats will be exposed to three heterologous
viruses: (i) a nonpathogenic retrovirus, FeSFV, (ii) an immunopathic
retrovirus, FeLV, and (iii) a DNA virus, FHV1. To study the effect of a
bacterial infection as an immune stimulant, living bacillus Calmette-Guerin
(BCG) vaccine will be used. Results from this investigation will determine whether immune activation
and heterologous infections activate FIV gene expression in vivo and if
FIV-infected cats can be used as an appropriate small animal model to study
mechanisms of in vivo immunopathogenesis in AIDS.
StatusFinished
Effective start/end date7/1/906/30/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

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

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