INTERFERON GAMMA AND CONTROL OF HCV REPLICATION

干扰素γ和HCV复制的控制

• 批准号: 8357654
• 负责人: Christopher M. Walker
• 金额: $ 3.21万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357654
• 关键词: Ascaridil; Cells; Chronic Hepatitis C; Data; Development; Event; Funding; Future; Grant; Hepatitis B Virus; Hepatitis C virus; Hepatology; Immune; Immune response; Immune system; In Vitro; Individual; Infection; Infection Control; Interferon Type II; National Center for Research Resources; Nature; Pan Genus; Play; Primates; Principal Investigator; Production; Research; Research Infrastructure; Resources; Role; Source; Staging; Supplementation; System; Transgenic Mice; United States National Institutes of Health; Vaccines; Viral; Virus; Virus Replication; Walkers; cost; cytokine; effective therapy; in vivo; killings; mouse model; pathogen; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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。