Although 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 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 Experimental conditions for detection of CMV-specific CTL activity, quantitation of CMV-specific proliferative precursor frequency and quantitation of CMV viral load in peripheral blood by QC-PCR were established in CMV-seropositive rhesus macaques A vigorous class I MHC-restricted and CD8+ T lymphocyte-mediated CMV-specific CTL response was detected in SIV-naive CMV-seropositive rhesus macaques and in chronically SIV-infected rhesus macaques with low SIV viral loads The frequency of CMV-specific proliferative T lymphocyte precursors ranged between one in 5,223 and one in 31,648 PBMC in two normal CMV-seropositive rhes us m acaques Two CMV-seropositive, tetanus-immunized rhesus macaques infected parenterally with SIVmac251 are being evaluated longitudinally for suppression of CMV-specific and recall antigen-specific immune responses and CMV reactivation Profound suppression of T helper cell function as evidenced by a 45 to 115-fold decrease in precursor frequency of CMV-specific proliferative T lymphocytes and a 3 to 20-fold decrease in precursor frequency of tetanus-specific proliferative T lymphocytes was evident in the first two weeks after SIV infection and was associated with a transient increase in buffy coat CMV viral DNA The loss in T helper cell function was present prior to marked peripheral CD4+ T lymphocytopenia CMV-specific CTL activity was decreased at 2 weeks and absent at 4 and 8 weeks after SIV infection By week 8 to 12 after SIV infection, though tetanus-specific proliferative activity had returned to baseline or greater levels, CMV-specific proliferative precursors had recover ed to less than 20% of the baseline values Surprisingly, recovery of CMV-specific CTL activity was evident at week 12, even in the absence of complete recovery of CMV-specific T helper cell function 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
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