Project: Research project

Project Details


Although HIV infection is generally associated with prolonged clinical
latency, an expanding body of evidence points to the importance of early
events for determining the outcome of HIV infection. Primary infection of
humans with HIV-1 is often associated with an acute mononucleosis-like
clinical syndrome characterized by fever, malaise, pharyngitis,
lymphadenopathy, headache, diarrhea, rash and meningoencephalitis and is
accompanied by a burst in virus replication detectable in the blood
approximately 1-3 weeks following exposure. The appearance of specific
antiviral immune responses is associated with dramatic reductions in the
level of viremia, but there is no clearance of the virus. Limitations
inherent in studying human subjects have precluded detailed investigation
of many of the early events critical for virus transmission, dissemination
and eventual disease progression. The SIV/macaque model will be used to
address these critical issues. Whether there is selective transmission of
particular SIV genotypes across the mucosal surface will be determined.
The initial cellular targets of primary infection by the mucosal and
intravenous routes will be identified and the sequential targets of the
spreading viral infection will be- characterized. Analyses will include
subsets of CD4+ lymphocytes and progenitor cells in thymus and bone marrow
as possible preferential targets. The influence of varying viral genotype
on transmission, dissemination to tissues and tissue-specific disease
manifestations will be investigated. Finally, the importance of cytotoxic
T lymphocytes for controlling the early burst in virus replication will be
investigated in this manipulable experimental setting. These studies will
be achieved through the cooperation of three principal investigators at
the New England Regional Primate Research Center with extensive experience
in the disciplines of Virology, Molecular Biology, Pathology and
Effective start/end date9/1/958/31/99


  • National Institute of Allergy and Infectious Diseases


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