gC1qR expression in chimpanzees with resolved and chronic infection: potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection.
gC1qR expression in chimpanzees with resolved and chronic infection: potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection.
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DOI：
10.1016/j.virol.2005.11.020
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发表时间：
2006-03
期刊：
影响因子：
3.7
通讯作者：
Z. Yao;M. T. Shata;Nancy Tricoche;M. Shan;B. Brotman;W. Pfahler;Y. Hahn;A. Prince
中科院分区：
文献类型：
--
作者：
Z. Yao;M. T. Shata;Nancy Tricoche;M. Shan;B. Brotman;W. Pfahler;Y. Hahn;A. Prince
黑猩猩是一种独特的HCV感染动物模型，其中约50%的感染会自发消退。据报道，康复的黑猩猩对HCV核心的T细胞反应的强度大于慢性感染的黑猩猩。然而，解决感染的黑猩猩克服核心介导的免疫抑制的机制仍然未知。在这项研究中，我们检测了HCV核心对解决和慢性HCV感染的黑猩猩T细胞反应性的影响。我们发现核心蛋白强烈抑制慢性感染黑猩猩的T细胞激活和增殖，而这种抑制作用在解决感染的黑猩猩中是有限的。值得注意的是，与慢性丙型肝炎病毒感染的黑猩猩相比，康复黑猩猩T细胞表面的gC1qR水平以及核心蛋白的结合水平较低。有趣的是，在HCV感染和康复的黑猩猩中，gC1qR表达水平和对核心诱导抑制的易感性的差异是在HCV攻击之前观察到的，这表明感染结果可能是遗传决定的。这些发现表明，T细胞表面的gC1qR表达对于HCV核心介导的T细胞抑制和病毒清除至关重要，这代表了病毒篡夺宿主机制以维持持久性的新机制。
Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence.