INTERFERON GAMMA AND CONTROL OF HCV REPLICATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前尚不清楚那些能够解决感染的个体控制并最终终止丙型肝炎病毒复制的机制，但对于生产这种病原体的有效疫苗和未来有效疗法的开发都是至关重要的。在转基因小鼠模型和黑猩猩的实验中，已经证明可以通过免疫细胞(Guidotti和Chisari)分泌细胞因子干扰素-γ来控制乙肝病毒的复制。Ann Rev免疫2001；19：65-89)，而不是要求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，干扰素-γ有助于控制丙型肝炎病毒的复制(Frese等人的肝病2002年；35：694703；Lanford等人J Virol 2003；77：1092-1104)。然而，这些体外数据并不一定反映体内的情况。已经开展了一项单一研究，研究补充干扰素-γ是否改变慢性丙型肝炎病毒感染的病毒复制(Shin等人。J Virol 2005；79：13412-30)；然而，感染病毒很可能已经从丙型肝炎病毒特异性反应中逃脱，而持续的丙型肝炎特异性免疫反应在感染的这个阶段是有缺陷的(Bowen和Walker)。《自然》2005；436：946-52)。因此，这一数据不太可能反映出干扰素-γ在自然控制感染的个体中所起的作用。

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.