Intrinsic susceptibility of rhesus macaque peripheral CD4+ T cells to simian immunodeficiency virus in vitro is predictive of in vivo viral replication
Intrinsic susceptibility of rhesus macaque peripheral CD4+ T cells to simian immunodeficiency virus in vitro is predictive of in vivo viral replication
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DOI：
10.1128/jvi.74.20.9388-9395.2000
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发表时间：
2000-10-01
影响因子：
5.4
通讯作者：
Hirsch, VM
中科院分区：
文献类型：
--
作者：
Goldstein, S;Brown, CR;Hirsch, VM
先前对恒河猴感染猿猴免疫缺陷病毒 (SIV) 的研究表明，外周血单核细胞 (PBMC) 对体外 SIV 感染的内在敏感性可预测 SIV 攻击后的相对病毒血症。本研究旨在评估一组由六只恒河猴组成的特征良好的队列，这些恒河猴在体外对 SIV 感染的易感性存在显着差异。在 1 年的评估期间，PBMC 对体外 SIVsmE543-3 感染的相对敏感性排序保持不变。不同供体的CD4(+) T细胞耗尽的PBMC、巨噬细胞和通过用疱疹病毒saimiri转化PBMC而衍生的CD4(+) T细胞系中保持了不同的敏感性，表明这种现象是CD4(+)靶细胞的固有特性。用 SIVsmE543-3 静脉感染这些猕猴后，我们观察到血浆病毒血症的范围很广，其顺序与体外研究建立的相对易感性相同。接种后2周和8周的血浆病毒血症与体外敏感性之间存在显着相关性（P < 0.05）。两只最易感的猕猴对 1 型猿猴 T 淋巴细胞病毒呈血清阳性，这一观察结果可能表明这种病毒感染在体外和体内增强对 SIV 感染的易感性方面发挥了作用。总之，CD4(+)靶细胞的内在敏感性似乎是影响体内早期病毒复制模式的重要因素，在使用SIV/猕猴模型进行疫苗研究的设计和解释时应考虑这一因素。
Previous studies with simian immunodeficiency virus (SIV) infection of rhesus macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (PBMC) to infection with SIV in vitro was predictive of relative viremia after SIV challenge. The present study was conducted to evaluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to SIV infection in vitro. Rank order relative susceptibility of PBMC to SIVsmE543-3-infection in vitro was maintained over a 1-year period of evaluation. Differential susceptibility of different donors was maintained in CD4(+) T-cell-depleted PBMC, macrophages, and CD4(+) T-cell lines derived by transformation of PBMC with herpesvirus saimiri, suggesting that this phenomenon is an intrinsic property of CD4(+) target cells. Following intravenous infection of these macaques with SIVsmE543-3, we observed a wide range in plasma viremia which followed the same rank order as the relative susceptibility established by in vitro studies. A significant correlation was observed between plasma viremia at 2 and 8 weeks postinoculation and in vitro susceptibility (P < 0.05). The observation that the two most susceptible macaques were seropositive for simian T-lymphotropic virus type 1 may suggests a role for this viral infection in enhancing susceptibility to SIV infection in vitro and in vivo. In summary, intrinsic susceptibility of CD4(+) target cells appears to be an important factor influencing early virus replication patterns in vivo that should be considered in the design and interpretation of vaccine studies using the SIV/macaque model.