Abstract

The broad long range objective is to understand the role of cellular adhesion molecules in the biology of HIV. The hypothesis is that functional cell adhesion molecules acquired by the virus can independently mediate binding of virus to cells, increase the avidity of CD4 mediated virus binding, and change virus tropism. The project will focus on three adhesion molecules: LFA-1, VLA-4, and CD44.
The specific aim are to: (a) Characterize the role of cell adhesion molecules in HIV transmission using expression vectors to change adhesion molecule phenotype of cells; (b) Evaluate the contribution of cell adhesion molecules to HIV tropism; (c) Characterize the effect of HIV infection on expression and function of adhesion molecules; (d) Determine if cell adhesion molecules are associated with HIV in vivo using plasma from MACS participants and well characterized plasmid HIV for acquired adhesion molecules; and (e) Define the role of LFA-1 in serum neutralization of HIV infection in primary T cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031806-05
Application #
2330367
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1991-09-01
Project End
2000-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Liao, Zhaohao; Graham, David R; Hildreth, James E K (2003) Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. AIDS Res Hum Retroviruses 19:675-87
Nguyen, Deborah Greene; Hildreth, James E K (2003) Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages. Eur J Immunol 33:483-93
Graham, David R M; Chertova, Elena; Hilburn, Joanne M et al. (2003) Cholesterol depletion of human immunodeficiency virus type 1 and simian immunodeficiency virus with beta-cyclodextrin inactivates and permeabilizes the virions: evidence for virion-associated lipid rafts. J Virol 77:8237-48
Banks, Nia D; Kinsey, Nicole; Clements, Janice et al. (2002) Sustained antibody-dependent cell-mediated cytotoxicity (ADCC) in SIV-infected macaques correlates with delayed progression to AIDS. AIDS Res Hum Retroviruses 18:1197-205
Speck, R Renae; Yu, Xiao-Fang; Hildreth, James et al. (2002) Differential effects of p-glycoprotein and multidrug resistance protein-1 on productive human immunodeficiency virus infection. J Infect Dis 186:332-40
Liao, Z; Cimakasky, L M; Hampton, R et al. (2001) Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. AIDS Res Hum Retroviruses 17:1009-19
Niyogi, K; Hildreth, J E (2001) Characterization of new syncytium-inhibiting monoclonal antibodies implicates lipid rafts in human T-cell leukemia virus type 1 syncytium formation. J Virol 75:7351-61
Liao, Z; Roos, J W; Hildreth, J E (2000) Increased infectivity of HIV type 1 particles bound to cell surface and solid-phase ICAM-1 and VCAM-1 through acquired adhesion molecules LFA-1 and VLA-4. AIDS Res Hum Retroviruses 16:355-66
Iyengar, S; Schwartz, D H; Clements, J E et al. (2000) CD4-independent, CCR5-dependent simian immunodeficiency virus infection and chemotaxis of human cells. J Virol 74:6720-4
Nguyen, D H; Hildreth, J E (2000) Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol 74:3264-72

Showing the most recent 10 out of 24 publications