INTERFERON GAMMA AND CONTROL OF HCV REPLICATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 HCV复制的控制机制，并最终终止那些能够解决感染的人仍然不清楚，然而，生产这种病原体的有效疫苗，并有效的治疗方法的未来发展是至关重要的。在转基因小鼠模型和黑猩猩中的实验中，已经证明可以通过免疫细胞分泌细胞因子IFN-γ来控制B型肝炎病毒复制（Guidotti和Chisari. Ann Rev Immunol 2001; 19：65-89），而不是需要通过免疫系统杀死感染细胞的病毒控制。使用体外系统的实验表明，IFN-γ可有助于控制HCV复制（Frese等Hepatology 2002; 35：694703; Lanford等人J Virol 2003; 77：1092-1104）。然而，该体外数据不一定反映体内事件。已经进行了一项研究，检查IFN-γ的补充是否改变慢性HCV感染中的病毒复制（Shin等J Virol 2005; 79：13412-30）;然而，很可能感染病毒已经从HCV特异性应答中逃逸，并且持续的HCV特异性免疫应答在该感染阶段是有缺陷的（Bowen和步行者。Nature 2005; 436：946-52）。因此，该数据不太可能反映IFN-γ在解决感染的个体中自然控制感染中所起的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mechanisms by which replication of HCV is controlled and eventually terminated by those individuals that are able to resolve infection remain unclear, however are of paramount importance both to the production of an effective vaccine for this pathogen, and to future development of effective therapies. In experiments in transgenic mouse models and the chimpanzee, it has been demonstrated that control of hepatitis B virus replication can be controlled by secretion of the cytokine IFN-gamma by immune cells (Guidotti and Chisari. Ann Rev Immunol 2001; 19: 65-89), rather than viral control requiring killing of infected cells by the immune system. Experiments using in vitro systems suggest that IFN-gamma could contribute to control of HCV replication (Frese et al Hepatology 2002; 35:694703; Lanford et al J Virol 2003; 77: 1092-1104). However this in vitro data does not necessarily reflect in vivo events. A single study has been carried out examining whether supplementation of IFN-gamma alters viral replication in chronic HCV infection (Shin et al. J Virol 2005; 79: 13412-30); however it is likely that both the infecting virus has escaped from HCV-specific responses and that persisting HCV-specific immune responses are defective by this stage of infection (Bowen and Walker. Nature 2005; 436: 946-52). This data is thus unlikely to reflect the role played by IFN-gamma in natural control of infection in individuals that resolve infection.