An essential step in the life cycle of HIV-1 and other retroviruses is the nuclear import of the preintegration complex, a replication intermediate carrying the viral genome. During the subsequent productive phase of the life cycle, Gag proteins, precursors to the structural proteins of the viral core, travel to the plasma membrane where virion assembly and release occur. The transport mechanisms involved in these aspects of retroviral replication have not been identified. In the life cycle of many viruses, elements of the cytoskeleton are involved in the transport of viral proteins and structures. They have found evidence that HIV-1 Gag proteins interact directly with the cytoskeleton. The general objective of this application is to further examine interactions between HIV-1 and the cytoskeleton and determine their role in viral replication. These interactions may be involved in cell to cell transmission of virus, in the assembly of virus particles, and determine the ability of HIV-1 replicate in certain cell types involved in disease pathogenesis.
The Specific Aims are: 1) to identify the cytoskeletal structures which interact with the HIV-1 Gag proteins, 2) to identify the HIV determinants of interaction with the cytoskeleton, and 3) to examine the role of the cytoskeleton in HIV-replication.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA072148-04
Application #
2895717
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
1999-08-10
Budget End
2000-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Krogstad, Paul; Geng, Yong-Zhi; Rey, Osvaldo et al. (2002) Human immunodeficiency virus nucleocapsid protein polymorphisms modulate the infectivity of RNA packaging mutants. Virology 294:282-8
Ibarrondo, F J; Choi, R; Geng, Y Z et al. (2001) HIV type 1 Gag and nucleocapsid proteins: cytoskeletal localization and effects on cell motility. AIDS Res Hum Retroviruses 17:1489-500