CMV SPECIFIC CELLULAR IMMUNITY & REACTIVATION FOLLOWING SIV INFECTION IN RHESUS

虽然CMV是艾滋病的重要病原体，但有关CMV的信息很少。 艾滋病毒如何影响CMV或CMV是否以及如何加速 艾滋病毒感染的过程SIV/猕猴模型是最主要的 艾滋病发病机制的动物模型，并允许检查 慢病毒和CMV在对照实验中的相互作用 CMV特异性CTL检测的实验条件 CMV特异性增殖前体的活性、定量 外周血中CMV病毒载量的频率和定量， 在CMV血清阳性恒河猴中建立了QC-PCR。 I类MHC限制性和CD 8 + T淋巴细胞介导的CMV特异性CTL 在SIV-幼稚CMV-血清阳性恒河猴中检测到应答 在慢性SIV感染的恒河猴中， CMV特异性增殖性T淋巴细胞频率 前体细胞在两个PBMC中的比例为5，223分之一至31，648分之一， 正常CMV-血清阳性猕猴两个CMV-血清阳性， SIVmac 251肠道外感染破伤风免疫猕猴 正在纵向评估CMV特异性抑制， 召回抗原特异性免疫反应和CMV再激活 抑制T辅助细胞功能，如通过45至115倍的 CMV特异性增殖性T细胞前体频率降低 淋巴细胞和前体频率降低3至20倍， 破伤风特异性增殖性T淋巴细胞在第一次 在SIV感染后两周， 血沉棕黄层CMV病毒DNA增加辅助性T细胞减少 在明显的外周CD 4 + T淋巴细胞减少症之前存在功能 CMV特异性CTL活性在2周时降低，在4周时不存在， SIV感染后8周SIV感染后8 - 12周， 尽管破伤风特异性增殖活性已经恢复， 基线或更高水平，CMV特异性增殖前体细胞具有 恢复艾德至小于基线值的20%令人惊讶的是， CMV特异性CTL活性的恢复在第12周是明显的，即使在 CMV特异性T辅助细胞没有完全恢复 功能阐明相互作用的基本机制， CMV和SIV应有助于设计有效的抗病毒药物或 以免疫为基础的治疗策略，以控制发病率 与艾滋病中CMV感染相关

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