Abstract

This is a study on a putative CMV-encoded superantigen (SAG). The applicant has previously shown that CMV infection induces the preferential proliferation of Vb12 T cells and that HIV preferentially infects SAG activated Vb12 T cells. The goals of this proposal are to identify the CMV-related SAG and to investigate the hypothesis that Vb12-bearing T cells are a reservoir for HIV infection and are resistant to apoptosis. In particular cloned SAG will be used to examine the expression, tissue distribution and homologies of the CMV SAG to other known SAGs and herpesvirus gene products. The investigator will examine the nature of HIV infection in Vb12 T cells as to the frequency of infected cells, their clonality, and whether they produce infectious virus. He will investigate whether SAG-stimulated Vb12 T cells are resistant to the induction of apoptosis and begin to explore possible mechanisms. Another aim is to investigate whether the SAG enhances CMV infection or reactivation. Finally a potential role of the CMV SAG in enhancing HIV infection will be explored.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI033322-04A1
Application #
2003863
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1993-04-01
Project End
2001-11-30
Budget Start
1996-12-15
Budget End
1997-11-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Weill Medical College of Cornell University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Hodtsev, A S; Choi, Y; Spanopoulou, E et al. (1998) Mycoplasma superantigen is a CDR3-dependent ligand for the T cell antigen receptor. J Exp Med 187:319-27
Liao, L; Marinescu, A; Molano, A et al. (1996) TCR binding differs for a bacterial superantigen (SEE) and a viral superantigen (Mtv-9). J Exp Med 184:1471-82
Bayard-McNeeley, M; Doo, H; He, S et al. (1996) Differential effects of interleukin-12, interleukin-15, and interleukin-2 on human immunodeficiency virus type 1 replication in vitro. Clin Diagn Lab Immunol 3:547-53
Lapa e Silva, J R; Linhares, C; Boechat, N et al. (1996) Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: evidence for new recruitment and cell activation. Mem Inst Oswaldo Cruz 91:389-94
Ho, J L (1996) Co-infection with HIV and Mycobacterium tuberculosis: immunologic interactions, disease progression, and survival. Mem Inst Oswaldo Cruz 91:385-7
Posnett, D N (1995) Environmental and genetic factors shape the human T-cell receptor repertoire. Ann N Y Acad Sci 756:71-80
Posnett, D N; Kabak, S; Dobrescu, D et al. (1995) The HIV-1 reservoir in distinct V beta subsets of CD4 T cells: evidence for a putative superantigen. J Clin Immunol 15:18S-21S
Dobrescu, D; Ursea, B; Pope, M et al. (1995) Enhanced HIV-1 replication in V beta 12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen. Cell 82:753-63
Ho, J L; He, S; Hu, A et al. (1995) Neutrophils from human immunodeficiency virus (HIV)-seronegative donors induce HIV replication from HIV-infected patients' mononuclear cells and cell lines: an in vitro model of HIV transmission facilitated by Chlamydia trachomatis. J Exp Med 181:1493-505
Dobrescu, D; Kabak, S; Mehta, K et al. (1995) Human immunodeficiency virus 1 reservoir in CD4+ T cells is restricted to certain V beta subsets. Proc Natl Acad Sci U S A 92:5563-7

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