The investigator proposes to extend previous findings in the SCID-hu mouse model of normal human thymopoiesis in which HIV infection causes loss of CD4+ thymocytes and pathology similar to that seen in infected persons.
The Specific Aims to be addresses are: 1) to more completely define the pathogenic mechanisms in operating in human thymocytes, 2) to determine the effects of HIV infection on thymic stromal elements, and 3) to determine the pathogenic potential of attenuated virus strains in vivo. Although thymic functions is most obvious in the developing fetus and in children, the investigator believe that these studies may have relevance to infected adult patients because recent clinical data suggest that naive T lymphocytes can be produced by adults following antiretroviral therapy. The investigator proposes that experiments addressing the pathogenic potential of viral mutants will help identify candidate live attenuated vaccine strains. It is suggested that these studies should further knowledge on the effect of HIV on human hematopoietic organs and help to understand how HIV causes the profound immunosuppression seen in AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI036059-08
Application #
6373391
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Young, Janet M
Project Start
1994-09-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
8
Fiscal Year
2001
Total Cost
$302,602
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
Vatakis, Dimitrios N; Nixon, Christopher C; Bristol, Gregory et al. (2009) Differentially stimulated CD4+ T cells display altered human immunodeficiency virus infection kinetics: implications for the efficacy of antiviral agents. J Virol 83:3374-8
Vatakis, Dimitrios N; Kim, Sanggu; Kim, Namshin et al. (2009) Human immunodeficiency virus integration efficiency and site selection in quiescent CD4+ T cells. J Virol 83:6222-33
Marsden, Matthew D; Xu, Jie; Hamer, Dean et al. (2008) Short communication: Activating stimuli enhance immunotoxin-mediated killing of HIV-infected macrophages. AIDS Res Hum Retroviruses 24:1399-404
Vatakis, Dimitrios N; Bristol, Gregory; Wilkinson, Thomas A et al. (2007) Immediate activation fails to rescue efficient human immunodeficiency virus replication in quiescent CD4+ T cells. J Virol 81:3574-82
Marsden, Matthew D; Zack, Jerome A (2007) Human immunodeficiency virus bearing a disrupted central DNA flap is pathogenic in vivo. J Virol 81:6146-50
Arlen, Philip A; Brooks, David G; Gao, Lian Y et al. (2006) Rapid expression of human immunodeficiency virus following activation of latently infected cells. J Virol 80:1599-603
Chang, Margaret; Brown, Helen J; Collado-Hidalgo, Alicia et al. (2005) beta-Adrenoreceptors reactivate Kaposi's sarcoma-associated herpesvirus lytic replication via PKA-dependent control of viral RTA. J Virol 79:13538-47
Kitchen, Scott G; Whitmire, Jason K; Jones, Nicole R et al. (2005) The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral and cellular antigens. Proc Natl Acad Sci U S A 102:3794-9
Kitchen, Scott G; Jones, Nicole R; LaForge, Stuart et al. (2004) CD4 on CD8(+) T cells directly enhances effector function and is a target for HIV infection. Proc Natl Acad Sci U S A 101:8727-32
Chen, Hongying; Zha, Junli; Gowans, Reginald E et al. (2004) Alcohol enhances HIV type 1 infection in normal human oral keratinocytes by up-regulating cell-surface CXCR4 coreceptor. AIDS Res Hum Retroviruses 20:513-9

Showing the most recent 10 out of 44 publications