This proposal will focus on central immunologic, virologic and molecular biologic mechanisms important in the progression and pathogenesis of AIDS. The Program consists of seven interrelated projects and three associated Core facilities which bring together basic and clinical scientists at the Columbia-Presbyterian Medical Center representing the departments of Medicine, Microbiology, Physiology, Biochemistry and Pathology. All of the project leaders are currently involved in basic research efforts highly relevant to AIDS pathogenesis, and the seven proposed projects represent logical extensions of this basic research. Some of the key questions that collectively we will attempt to answer include: (1) Which subsets of cells are initially infected by HIV and provide the cellular reservoir for latent viral infection? (2) Which cellular proteins and receptors in consort with or in lieu of CD4 are involved in viral penetrance and infectivity? (3) What virologic and immunologic mechanisms conspire to activate HIV intracellularly in T4 cells or monocytes and induce the spread of virus? (4) Which HIV genes are crucial for viral penetration, integration and activation? (5) What is the effect of the expression of a variety of HIV genes on the activation and control of cellular genes and cell function? The project leaders in this Program have expertise representing a variety of scientific areas including T cell and macrophage immunobiology and biochemistry, molecular viral pathogenesis, retrovirology and clinical infectious disease. The intent of this Program Project will be to focus the intellectual and technologic resources of these investigators and their disciplines on the solution to the questions outlined above which we feel are essential to understanding AIDS pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
3P01AI026886-05S1
Application #
3091930
Study Section
Special Emphasis Panel (SRC (90))
Project Start
1988-09-01
Project End
1994-02-28
Budget Start
1992-09-01
Budget End
1994-02-28
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Karpusas, M; Hsu, Y M; Wang, J H et al. (1995) 2 A crystal structure of an extracellular fragment of human CD40 ligand. Structure 3:1031-9
Lowy, I; Caruso, M; Goff, S P et al. (1994) Cellular thymidine kinase activity is required for the inhibition of HIV-1 replication by AZT in lymphocytes. Virology 200:271-5
Covey, L R; Cleary, A M; Yellin, M J et al. (1994) Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand. Mol Immunol 31:471-84
Lederman, S; Yellin, M J; Cleary, A M et al. (1994) The understanding of contact-dependent T-cell helper function in molecular, cellular and physiological detail. Res Immunol 145:215-21;discussion 244-9
Lederman, S; Yellin, M J; Cleary, A M et al. (1994) T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death. J Immunol 152:2163-71
Hotta, J; Shi, L; Ginsberg, H S (1994) Effect of CD4 gene expression on adenovirus replication. J Virol 68:7284-91
Thomas, C A; Dobkin, J; Weinberger, O K (1994) TAT-mediated transcellular activation of HIV-1 long terminal repeat directed gene expression by HIV-1-infected peripheral blood mononuclear cells. J Immunol 153:3831-9
Cao, C; Steinberg, T H; Neu, H C et al. (1993) Probenecid-resistant J774 cell expression of enhanced organic anion transport by a mechanism distinct from multidrug resistance. Infect Agents Dis 2:193-200
Patrick, S L; Wright, T C; Fox, H E et al. (1993) Human immunodeficiency virus infection of early passage cervical epithelial cultures. Int J STD AIDS 4:342-5
Lederman, S; Yellin, M J; Covey, L R et al. (1993) Non-antigen signals for B-cell growth and differentiation to antibody secretion. Curr Opin Immunol 5:439-44

Showing the most recent 10 out of 22 publications