STUDY OF MHC &CTL IN OPIATE-DEPENDENT MONKEYS WITH AIDS

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from Applicant's Abstract) Simian immunodeficiency virus
(SIV) infection of macaques provides the best non-human primate model for
studying AIDS. These investigators will utilize the SIV/macaque model to
determine whether nef-specific cytotoxic T lymphocytes (CTL) play a role in
selection for new virus variants in vivo. The investigators will also test the
hypothesis that clones of virus-specific CTL can persist for the entire course
of the virus infection. Additionally, they will determine whether the MHC of
the rhesus macaque can play a role in resistance to SIV infection in vivo.
Finally, they will investigate whether opiates can influence the generation of
AIDS virus-specific CTL or helper T lymphocyte (HTL) responses during the
course of AIDS virus infection in vivo. These studies will be carried out using
blood samples obtained from an ongoing NIH-supported study aimed at determining
how opiate-dependency alters progression of AIDS induced by SIV smm9 in 40
rhesus macaques.

In Specific Aim 1 they will test the hypothesis that the nef-specific CTL
response selects for new viral variants and that these new variants escape CTL
recognition. They have recently generated preliminary data indicating that CTLs
exert considerable selective pressure on nef, whereas selective pressure on env
CTL epitopes was more relaxed.

In Specific Aim 2 they will test the hypothesis that clones of CTL generated
early in the course of SIV infection persist for the entire course of the
disease. Dr. McMichael's group have preliminary data suggesting that clones of
T cells can persist during SIV infection. This is somewhat contrary to previous
findings.

In Specific Aim 3 they will test the hypothesis that certain MHC alleles can
influence the course of SIVsmm9 infection in vivo. Since products of the MHC
genes bind pathogen-derived peptides and present them to T cells, it has been
suggested that these highly polymorphic molecules might influence how 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.

In Specific Aim 4, they will test the hypothesis that opiates can influence CTL
or HTL responses which can, in turn, determine the course of disease after
infection. Although evidence exists for the role CTLs and HTLs in HIV
infection, it has been difficult to carry out long term studies in individuals
in which time of infection, and dose and nature of the virus are known in a
relevant animal model. In this cohort of animals they will be able to determine
whether opiates can influence the cellular immune response to the AIDS virus.
StatusFinished
Effective start/end date9/30/998/31/03

Funding

  • National Institute on Drug Abuse: $328,960.00
  • National Institute on Drug Abuse: $21,200.00
  • National Institute on Drug Abuse: $319,379.00
  • National Institute on Drug Abuse: $338,829.00

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