FUNCTION FOR VPR AND VPX OF PRIMATE LENTIVIRUSES

Project: Research project

Project Details

Description

DESCRIPTION (adapted from the Abstract): The CD4+ T cells and
macrophages represent the primary targets for infection with HIV-1.
Replication of HIV-1 within macrophages plays a fundamental role in
virus transmission, in the sequestration of HIV-1 in tissues, and in the
maintenance of HIV-1 persistence during the progression of disease.
Although macrophages are terminally differentiated and non-dividing
cells, mitosis is not required for productive infection by lentiviruses,
such as HIV-1, in contrast to onco-retroviruses which do require host
cell mitosis for nuclear localization of viral DNA and provirus
establishment. The infection of non-dividing cells by HIV-1 is governed
by the association of virion-derived nucleophilic proteins with the
viral genome, which facilitate nuclear localization of the viral genome
in non-dividing cells. The Principal Investigator and his associates
have shown that the nucleophilic virion protein Vpr remains associated
with viral nucleic acids after virus infection and, as a consequence,
facilitates nuclear localization of viral DNA in non-dividing cells.
In this project, the Investigator proposes to characterize the mechanism
by which Vpr and the related virion protein Vpx of HIV-2 and SIV
determine nuclear localization of viral DNA and establish the provirus
in non-dividing host cells. He and his associates will: (1)
characterize determinants which govern nuclear localization of Vpr and
Vpx and derive infectious molecular clones of HIV-1 and HIV-2 containing
amino acid substitutions which preclude nuclear localization of Vpr and
Vpx; (2) examine the replication phenotype of HIV-1 Vpr and HIV-2
Vpr/Vpx nuclear localization mutants in primary lymphocytes and
macrophages, and the role of these proteins in nuclear targeting of viral
DNA and in provirus establishment in these cell systems; and (3)
identify the virion factors necessary for association of Vpr and Vpx
with viral nucleic acids within the viral nucleoprotein preintegration
complex.
StatusFinished
Effective start/end date5/1/954/30/00

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

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