CTLS AND MHC IN RESISTANCE TO SIV IN VIVO

Project: Research project

Project Details

Description

DESCRIPTION: Simian immunodeficiency virus (SIV) infection of macaques is
an excellent model for studying AIDS. Sequence similarities to HIV and the
ability to induce AIDS in macaques make SIVs and their infection of these
monkeys particularly important models for understanding the immune response
to the AIDS virus. They will utilize the SIV/macaque model to determine
whether the generation of AIDS virus-specific CTLs can be protective against
or can alter the course of AIDS virus infection in vivo. Furthermore, they
will determine whether the MHC of the rhesus macaque can play a role in
resistance to SIV infection.

CTLs are critical for containment of viral disease progression in
HIV-infected individuals. CTLs are important during the later courses of
individuals infected with HIV and the rapid decline in CTL activity often
presages the terminal disease stage. CTLs may also provide protection
against infection. It has recently been shown that vaccination with a
vaccinia construct expressing the SIV nef gene was sufficient to protect a
cynomolgus monkey from SIV infection. High levels of CTL activity were
correlated with ability to delay viremia in an additional two animals in
this study. These observations provide the rationale to determine whether
pre-existing CTLs can either prevent infection or modulate the course of
disease post-infection. Although strong evidence exists for the important
role of CTLs in HIV infection, it has been difficult to carry out definitive
in vivo experiments. At the Wisconsin Regional Primate Research Center,
they have recently defined 10 MHC-identical sibling pairs of rhesus monkeys
for these kinds of experiments and have also initiated a breeding program to
generate MHC-identical rhesus monkeys. They will, therefore, test the
hypothesis that CTLs can protect individuals from AIDS-virus infection, and
that CTLs can modulate the course of virus infection. They will use
MHC-identical sibling pairs to test this hypothesis.

Since the products of MHC genes bind pathogen-derived peptides and present
them to T cells it has been suggested that these highly polymorphic
molecules might influence he fashion in which an individual makes a response
to the AIDS virus. Recent studies have indicated that certain HLA molecules
may play an important role in long-term non-progressors. The investigators
will also test the hypothesis that certain MHC haplotypes or MHC molecules
can influence the course of SIV in vivo using sequence-based typing of
rhesus macaque MHC class I and II alleles.
StatusFinished
Effective start/end date8/1/977/31/00

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases

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