Human immunodeficiency virus type 1 (HIV-1) causes a slowly progressive deterioration of the immune system, resulting in the acquired immunodeficiency syndrome (AIDS). The mean period of time between infection with the virus and the onset of AIDS is eight to ten years. A major contributing factor to this long clinical latency period is likely to be related to latent or persistent states of the virus. When HIV-1 infects quiescent T-lymphocytes, virus is not produced until the cell is subsequently stimulated by mitogen or antigen. Thus, a latent form of the virus appears to exist in these cells. I have previously shown, using a quantitative polymerase chain reaction (PCR) technique, that reverse transcription of HIV-1 is arrested in quiescent T- lymphocytes. The objective of this proposal is to more fully understand the pathogenesis of HIV-1 by exploring the viral and cellular mechanisms responsible for the arrest of reverse transcription in quiescent T- lymphocytes. This work will: 1) further define the structure of the partial HIV-1 reverse transcripts in quiescent T-lymphocytes, and determine their role in pathogenesis; 2) determine the role of T-cell activation in reverse transcription; and 3) determine the mechanism of action responsible for the arrest of reverse transcription in quiescent T-lymphocytes. As more than 90% of circulating T-lymphocytes in vivo are in the quiescent state, these studies are of critical importance for understanding HIV-1 pathogenesis, and may identify novel approaches to test therapeutically.

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 #
5R29AI033259-03
Application #
2068259
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Cole, Steve W; Yan, Weihong; Galic, Zoran et al. (2005) Expression-based monitoring of transcription factor activity: the TELiS database. Bioinformatics 21:803-10
Cole, Steve W; Galic, Zoran; Zack, Jerome A (2003) Controlling false-negative errors in microarray differential expression analysis: a PRIM approach. Bioinformatics 19:1808-16
Cole, Steve W; Kemeny, Margaret E; Fahey, John L et al. (2003) Psychological risk factors for HIV pathogenesis: mediation by the autonomic nervous system. Biol Psychiatry 54:1444-56
Cole, S W; Naliboff, B D; Kemeny, M E et al. (2001) Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity. Proc Natl Acad Sci U S A 98:12695-700
Kaminski, N; Allard, J D; Pittet, J F et al. (2000) Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc Natl Acad Sci U S A 97:1778-83
Cole, S W; Jamieson, B D; Zack, J A (1999) cAMP up-regulates cell surface expression of lymphocyte CXCR4: implications for chemotaxis and HIV-1 infection. J Immunol 162:1392-400
Korin, Y D; Zack, J A (1999) Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes. J Virol 73:6526-32
Gong, J; Stenger, S; Zack, J A et al. (1998) Isolation of mycobacterium-reactive CD1-restricted T cells from patients with human immunodeficiency virus infection. J Clin Invest 101:383-9
Cole, S W; Korin, Y D; Fahey, J L et al. (1998) Norepinephrine accelerates HIV replication via protein kinase A-dependent effects on cytokine production. J Immunol 161:610-6
Korin, Y D; Zack, J A (1998) Progression to the G1b phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J Virol 72:3161-8

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