EVALUATION OF SIV/HIV CHIMERAS

Project: Research project

Project Details

Description

Human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-20 are T-
lymphocytopathic lentiviruses that cause AIDS. HIV-1 infections are
prevalent in many parts of the world. In vitro studies have shown that
the HIV-1 envelope (ENV) gene controls cell tropism, replication
kinetics, and cytopathicity. In addition, the env glycoprotein is a
target for anti-viral immune responses, and a high degree of sequence
variation in env is observed in both interpatient and intrapatient
isolates. Currently, animal models to directly investigate HIV-1
infection, functions of viral gene, and pathogenesis are very limited.
Several isolates of simian immunodeficiency virus (SIV) as well as some
molecular clones of SIV produce a fatal AIDS-like disease in Asian
macaques. HYPOTHESIS: The hypothesis is that the role(s) of the HIV-1
env gene in infection can be investigated by constructing recombinant
viruses (i.e., chimeras) between SIV and HIV-1 (designated SHIV) and
testing these recombinants in rhesus macaques. The env genes of four
HIV-1 clones that demonstrate different in vitro properties will be used
to replace the env gene of the pathogenic SIVmac239 clone to produce four
SHIV chimeras. SPECIFIC AIM 1: The objective is to identify an SHIV that
persists in experimentally infected juvenile macaques. Viral load, anti-
viral immune responses, and clinical signs will be monitored. SPECIFIC
AIM 2; The objective is to analyze cell and tissue distribution of the
four SHIVs in macaques. These experiments will determine whether in
vitro properties controlled by HIV-1 env correlate with in vivo
properties. SPECIFIC AIM 3: The objective is to assess sequence changes
in the HIV-1 env gene of SHIVs in infected macaques. Viruses will be
recovered from various tissues in infected animals, and sequence changes
in the env gene(s) will be analyzed. SPECIFIC AIM 4: The objective is
to augment the potential pathogenicity of SHIV. The SHIV chimeras will
be serially passaged in very young macaques. SIGNIFICANCE: A major goal
of this project is to establish a non-human primate model to determine
the significance of in vitro properties controlled by HIV-1 env gene.
In addition, patterns of HIV-1 env gene variation will be analyzed in the
animal model. This information may provide insight on mechanisms of
selection of viral variant in the host and may also provide a primate
system for testing immunogens that elicit protective immune responses
against HIV-1.
StatusFinished
Effective start/end date6/30/936/30/97

Funding

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

ASJC

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

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