lentiviruses, including the human immunodeficiency virus type 1 (HIV-1), are unusual among retroviruses in their ability to infect non-dividing cells. Because at any given time most T lymphocytes in the body are quiescent, and because tissue macrophages constitute the other important virus reservoir in a patient, it is likely that this property is essential for the spread of the virus in HIV-1 infected individuals, and for AIDS pathogenesis. As such, it constitutes a suitable target for novel antiviral therapies, whose development will require understanding the molecular events involved in this process. The proposed studies aim at providing this knowledge, by dissecting the mechanisms by which HIV-1 infects non-proliferating cells. Our preliminary work has shown that critical determinants in the viral MA and Vpr proteins are essential for HIV-1 infection of macrophages and growth-arrested cells, as well as for the establishment of a stable infection intermediate in quiescent T lymphocytes. We will extend these findings, by concentrating on the following specific aims; 1) Characterize the infection intermediate established by HIV-1 in quiescent T lymphocytes, as it is likely to play a pivotal role in the spread of the virus in vivo. 2) Map all the elements which participate in allowing HIV-1 infection of non-dividing cells. 3) Determine the significance of MA phosphorylation, a modification which we show is a key regulator of HIV-1 nuclear import. 4) Further investigate the contribution of Vpr to HIV-1 infection of non- proliferating cells, and elucidate Vpr mechanism of action. 5) Pursue studies which have allowed to detect a cellular MA-binding protein, possibly a chaperone responsible for escorting HIV-1 to the nucleus of non-dividing cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI037510-01A1
Application #
2074272
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1995-04-01
Project End
1999-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037