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Opioid
abuse has been postulated as a cofactor in the immunopathogenesis of
human immunodeficiency virus (HIV) infection and AIDS in the United
States and other countries. However, conflicting reports in human
studies claiming both survival advantage and disadvantage have been
described in the setting of drug abuse. We developed the non-human
morphine-dependent primate model of HIV/AIDS in Indian rhesus macaques
in order to circumvent major issues in human studies. In this model we
use a mixture of three viruses that lead to massive CD4+ T cell loss and
neurological disorders mimicking what happens in the human host. Studies
demonstrated that the morphine-dependent animals exhibited higher viral
loads. In addition, a fraction of the morphine-dependent macaques
developed an accelerated form of SIV/SHIV induced disease and died
within 20 weeks.
Based on these observations we hypothesize that morphine may exacerbate
SIV/SHIV infection and contribute to the early onset of the disease. We
also hypothesize that morphine may potentiate viral evolution. The
present application is designed to address these vital questions in our
SIV/SHIV macaque model of AIDS. This model of HIV/AIDS has been
successfully used in our laboratory to study viral pathogenesis. The
experiments in this proposal are designed to further expand our work in
the characterization of morphine contribution to SIV/SHIV evolution and
disease progression. In specific aims 1 and 2 we will compare
pre-infection and post-infection samples in the morphine-dependent vs.
control macaques in terms of humoral and cellular responses. This will
be followed by specific aim 3 in which we will determine the
differential viral migration and distribution. Finally, in specific aim
4 we will focus on the sequence analysis of the envelope and tat genes
of SIV in various tissue compartments.
These studies will not only help us to better understand the accelerated
form of the disease, viral evolution and distribution, but may also
refine the development of vaccines and antivirals.
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