K23: MOLECULAR BASIS OF INTERFERON RESPONSE IN HCV

该子项目是利用 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 中心，不一定是研究者的机构。 拟议的研究将调查的假设，治疗前的NS 5A区序列变异和丙型肝炎病毒（HCV）准种的多样性随着时间的推移减少与干扰素（IFN）治疗期间病毒滴度的第一阶段下降更快。 为了验证这一假设，我们提出了以下具体目标：1。定义已知对HCV治疗反应较低的患者人群中的第1和第2阶段病毒衰减。 我们将比较非裔美国人与高加索人以及HIV/HCV与HCV的HCV动力学。 患者将平均分布在非洲裔美国人和高加索人之间，这些人单独感染HCV基因型1或合并HIV感染。 患者将接受聚乙二醇化IFN和利巴韦林（RBV）治疗，作为标准治疗。 病毒衰变动力学分析将用于进一步确定早期治疗应答与种族或HIV状态之间是否存在关系。 2.确定HCV NS 5A编码区序列多样性与早期病毒衰减和IFN治疗结果的关系。 使用特定目标1中的样本，我们将研究干扰素治疗第1阶段期间HCV-NS 5A序列复杂性和多样性的时间动态。

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.