Sooty mangabey monkeys (SM) naturally infected with SIV maintain normal levels of CD4+ lymphocytes and do not develop AIDS despite chronic high level viral replication, short longevity of infected CD4+ T cells, and increased rates of CD4+ T cell turnover. Interestingly, despite otherwise intact immune functions, SIV-infected SMs manifest limited or absent anti-SIV specific cytotoxic T cell (CTL) responses. We have further shown that SIV-infected SMs possess preserved bone marrow, thymic and peripheral lymphoid sources for T lymphocyte production, and manifest levels of immune activation and apoptosis far lower than those seen in pathogenic infections with SIV in rhesus macaques (RMs) and with HIV in humans. These data suggest that the direct consequences of high level virus replication alone cannot account for the progressive CD4+ T cell depletion leading to AIDS. Rather, SIV-infected SMs may be spared, by their failure to mount significant antiviral immune responses, much of the bystander damage seen in pathogenic primate lentivirus infections that contributes to both accelerated CD4+ depletion and compromised host immune regenerative capacity. We propose to test the hypothesis that the type and magnitude of the host immune response to virus infections determines whether of not disease occurs by (1) detailed characterization of primary SIV infection in RMs and SMs by virologic, immunologic and genetic methods, (2) induction of active cellular anti-SIV immunity in acutely-infected SMs and evaluation of whether disease develops in an otherwise refractory host, and (3) blockade or deviation of host cellular immune responses to SIV in acutely-infected RMs, and evaluation of whether protection from disease progression is achieved in an otherwise susceptible host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049155-02
Application #
6511452
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Young, Janet M
Project Start
2001-03-01
Project End
2006-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
2
Fiscal Year
2002
Total Cost
$758,626
Indirect Cost
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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