The sera of HIV-infected individuals often do not show evidence of neutralization, either against laboratory strains of the virus or their homotypic isolate. Instead, these sera frequently enhance HIV infection in several cell types including human lymphocytes, macrophages and fibroblasts. The antibodies which are responsible for this phenomenon could play a role in increasing the spread of HIV in the host and the eventual destruction of immune cells. Antibody-dependent enhancement (ADE) of HIV seems to proceed independent of the CD4 receptor, and this process in macrophages appears to be mediated by the Fc receptor. However, the mechanism for enhancement in other cell types has not been defined, and the particular epitope(s) of HIV proteins involved in enhancement have not been identified. The objectives of this research proposal are to define the mechanisms by which HIV infect CD4+ lymphocytes and fibroblasts through serum enhancement, to identify the viral proteins involved in the ADE process and to determine the relative role of complement and Fc receptors in this process. The importance of ADE in the progression to AIDS will also be evaluated. Finally, the possible involvement of ADE in bringing about superinfection of HIV- infected cells and generation of recombinant virus will be examined. The information gained from these studies should be critical for the development of a safe and effective HIV vaccine, and could be helpful for approaches aimed at limiting HIV spread in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029394-04
Application #
3144196
Study Section
Special Emphasis Panel (ARR (V3))
Project Start
1989-09-30
Project End
1993-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143