The vif protein is likely to play an essential role during natural infections by HIV-1 and other lentiviruses. Vif is a critical determinant of virus infectivity. The biological function of vif and its mechanism of action are unknown. We have shown that vif enhances viral infectivity during virus production. We have also demonstrated that the effect of vif is associated with altered processing conformation of the HIV-1 envelope glycoproteins.
The aim of this proposal is to determine role of vif in virus transmission and to elucidate its mechanism of action. The effect of vif on the conformation, processing, transport, and assembly of the envelope and gag proteins will be examined to determine the effects of vif during virus production. The effect of vif on the efficiency of virus entry and reverse transcription will be examined to elucidate why virus produced in the presence of vif is more easily transmitted. The subcellular localization of vif will be examined since the localization of vif in the host cell is likely to yield insights into its function. The effects of inhibitors of protein processing and transport will be investigated to elucidate intracellular events and virus host-cell interactions which affect viral infectivity during virus production. It is anticipated that understanding the function of vif will lead to insights into mechanisms which are critical for the transmission of HIV-1 and other lentiviruses and may lead to the development of therapeutic strategies which could inhibit virus transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29AI033837-01
Application #
3456323
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1992-12-01
Project End
1997-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
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Yang, X; Goncalves, J; Gabuzda, D (1996) Phosphorylation of Vif and its role in HIV-1 replication. J Biol Chem 271:10121-9
Goncalves, J; Shi, B; Yang, X et al. (1995) Biological activity of human immunodeficiency virus type 1 Vif requires membrane targeting by C-terminal basic domains. J Virol 69:7196-204
Hoglund, S; Ohagen, A; Lawrence, K et al. (1994) Role of vif during packing of the core of HIV-1. Virology 201:349-55
Goncalves, J; Jallepalli, P; Gabuzda, D H (1994) Subcellular localization of the Vif protein of human immunodeficiency virus type 1. J Virol 68:704-12
Gabuzda, D H; Li, H; Lawrence, K et al. (1994) Essential role of vif in establishing productive HIV-1 infection in peripheral blood T lymphocytes and monocyte/macrophages. J Acquir Immune Defic Syndr 7:908-15