In the previous funding period, we have used the SIV infection/rhesus macaque animal model to investigate factors contributing to CMV pathogenesis in AIDS. In the next grant period, we propose to examine mechanisms of loss of CMV-specific immunity in AIDS. We hypothesize that SIV-mediated loss of CMV-specific CD4 v T cell help is necessary for loss or dysfunction of CMV-specific CD8 v T lymphocytes and memory B lymphocytes in rhesus macaques that develop AIDS. The SIV-induced loss of immune control of latent CMV infection may be due to a combination of destruction, impaired differentiation or effector function, and impaired homing of CMV-specific lymphocytes to tissue sites of CMV reactivation. Insight into mechanisms by which SIV infection affects CMV-specific immune responses will be valuable for understanding how immunological memory is disrupted in HIV-infected humans.
Our specific aims are as follows:
Specific Aim #1 : To investigate whether SIV infection of CMV-specific CD4 + T lymphocytes is a predictor of their decline in rhesus macaques with AIDS.
Specific Aim #2 : To determine whether the SIV-related decline in CMV-specific CD8 +T lymphocyte responses is secondary to depletion and/or functional anergy associated with loss of CD4 + T cell help.
Specific Aim #3 : To examine mechanisms of restoration of CMV-specific immunity in SIV-infected macaques treated with HAART.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043890-08
Application #
7005668
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Young, Janet M
Project Start
1998-07-01
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
8
Fiscal Year
2006
Total Cost
$412,571
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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Gauduin, Marie-Claire; Kaur, Amitinder; Ahmad, Shabbir et al. (2004) Optimization of intracellular cytokine staining for the quantitation of antigen-specific CD4+ T cell responses in rhesus macaques. J Immunol Methods 288:61-79
Mueller, Nicolas J; Livingston, Christine; Knosalla, Christoph et al. (2004) Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation. J Infect Dis 189:1628-33
Kaur, Amitinder; Kassis, Nadine; Hale, Corrina L et al. (2003) Direct relationship between suppression of virus-specific immunity and emergence of cytomegalovirus disease in simian AIDS. J Virol 77:5749-58

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