Differences in the ability of human immunodeficiency virus type 1 (HIV-1) isolates and strains to infect different CD4+ T-cell types have been noted for several years. These differences, in some cases, have been correlated with AIDS presentation and/or progression. There have been only limited systematic studies to date investigating the basis for differences in CD4+ T-cell tropism. The major limitation to such studies has been the lack of availability of molecularly clones isolates having different phenotypes for comparative studies. We have molecularly cloned an isolate of HIV-1, termed HIV-1JR-CSF, which is completely restricted in its ability to productively infect CD4+ T-cell lines such as Jurkat, CEM, A3.01, HPB-ALL, and HUT 78 in vitro, but maintains the ability to infect primary peripheral blood T-cells efficiently. Initial studies suggest that this restriction is a function of viral entry processes, and indicate that the presence of CD4 is not sufficient for viral infection. The studies proposed in this application further investigate the molecular basis for the differences in tropism between HIV-1JR-CSF and other isolates of HIV. An understanding of restricted infection for CD4+ T-cells may provide therapeutic leads to block HIV infection at the same level of restriction.
The Specific Aims are: 1. To determine the genetic basis for the inability of HIV-1JR-CSF to infect CD4+ T-cell lines. 2. To investigate the biochemical basis of HIV-1 CD4+ T-cell tropism, initially investigating the role of the env gene in HIV-1JR-CSF infection. 3. To investigate the basis for differences in susceptibility of cells to infection by HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI031822-01A1
Application #
3146819
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1992-02-01
Project End
1997-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Planelles, V; Bachelerie, F; Jowett, J B et al. (1995) Fate of the human immunodeficiency virus type 1 provirus in infected cells: a role for vpr. J Virol 69:5883-9
Planelles, V; Haislip, A; Withers-Ward, E S et al. (1995) A new reporter system for detection of retroviral infection. Gene Ther 2:369-76
Jowett, J B; Planelles, V; Poon, B et al. (1995) The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol 69:6304-13