K23: MOLECULAR BASIS OF INTERFERON RESPONSE IN HCV

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。 这项拟议的研究将调查这样一种假设，即治疗前NS5A区序列的变化和丙型肝炎病毒准种多样性随时间的减少与干扰素治疗期间病毒滴度的第一阶段下降速度更快有关。为了验证这一假设，我们提出了以下具体目标：1.确定已知对丙型肝炎病毒治疗反应较低的患者群体中的第一和第二阶段病毒衰变。我们将比较非裔美国人和高加索人的丙型肝炎病毒动力学，以及艾滋病毒/丙型肝炎病毒和丙型肝炎病毒。患者将在非裔美国人和高加索人之间平均分配，这些人单独感染丙型肝炎病毒或同时感染艾滋病毒。患者将接受聚乙二醇化干扰素和利巴韦林(RBV)治疗，作为标准护理。病毒衰变动力学分析将被用来进一步确定治疗的早期反应与种族或艾滋病毒状况之间是否存在关系。2.确定丙型肝炎病毒NS5A编码区序列多样性与病毒早期衰变及干扰素治疗结果的关系。使用在特定目标1中获得的样本，我们将检查干扰素治疗第一阶段期间丙型肝炎病毒NS5A序列的时间动力学复杂性和多样性。

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 proposed research will investigate the hypothesis that pre-treatment sequence variation of NS5A region and the decrease in diversity of Hepatitis C Virus (HCV) quasispecies over time is associated with a faster 1st phase decline in viral titer during interferon (IFN) therapy. To test this hypothesis, we have proposed the following specific aims: 1. Define the 1st and 2nd phase viral decay in patient populations known to have lower responses to HCV therapy. We will compare HCV kinetics of African Americans to Caucasians as well as HIV/HCV to HCV. Patients will be equally distributed between African Americans and Caucasians infected with HCV genotype 1 alone or with concurrent HIV infection. Patients will be treated with pegylated IFN and ribavirin (RBV), as standard of care. Viral decay kinetic analysis will be used to further define whether there is a relationship between early responses to therapy and race or HIV status. 2. Determine the relationship of HCV sequence diversity in the NS5A -coding region with the early phase viral decay and the outcome of IFN therapy. Using the samples derived in Specific Aim 1, we will examine the temporal dynamics of HCV-NS5A sequence complexity and diversity during the 1st phase of interferon therapy.