Although cytomegalovirus (CMV) is an important pathogen in AIDS, little information is available on how HIV affects CMV or whether and how CMV accelerates the course of HIV infection. In vivo studies that address these issues have not been forthcoming in human subjects. The SIV/macaque model is the leading animal model for AIDS pathogenesis and allows examination of the interactions between lentiviruses and CMV in a controlled experimental setting. We have established quantitative techniques for measuring CMV-specific cellular immunity and CMV viral load in rhesus macaques. We hypothesize that: (1) in SIV infection, CMV viremia and organ disease result primarily from reactivation of latent CMV infection consequent to SIV-induced suppression of host CMV-specific immune responses. (2) Increases in CMV viral load occur early in SIV infection and may independently accelerate SIV progression by enhancing SIV replication. We therefore propose to study interactions between CMV and SIV in rhesus macaques.
Our specific aims are: (1) To examine if CMV reactivation during SIV infection is temporally associated with suppression of CMV-specific immunity. (2) To evaluate if high SIV viral loads correlate with suppression of CMV-specific immunity and whether the immunosuppression is reversible on inhibiting SIV replication. (3) To determine if the course of SIV infection is accelerated in CMV-seropositive as compared to CMV-seronegative rhesus macaques. (4) To evaluate if CMV infection of SIV-infected CMV-seronegative rhesus macaques results in sustained increases in SIV load or accelerates the course of SIV infection and to investigate immune mechanisms associated with increased SIV loads. The elucidation of mechanisms underlying interactions between CMV and SIV should help in the design of effective antiviral or immune-based therapeutic strategies to control the morbidity associated with CMV infection in AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043890-02
Application #
2887859
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Plaeger, Susan F
Project Start
1998-07-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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