RACIAL DIFFERENCE IN HCV/HOST INTERACTIONS

田纳西大学孟菲斯丙型肝炎合作研究中心将使用HCV/宿主相互作用的研究来确定为什么非裔美国HCV患者对标准治疗（干扰素和利巴韦林）反应不佳。丙型肝炎很常见，占所有美国人的1.8%，但在非裔美国人和贫困人口中更为常见。在孟菲斯，55%的人口是非裔美国人，其中34%的人生活在贫困线以下。在之前的一项研究中，我们记录了该人群的反应率仅为5%，而白人的反应率为40%。我们建议通过HCV细胞配体/受体的等位基因变异系统地表征非裔美国人和白人之间的差异（项目1）。在项目2中，我们将继续开发一个体外系统来研究HCV， HCV是一种嵌合VSV病毒，其表面表达了丙型肝炎E1和E2包膜蛋白。我们将使用该模型来表征病毒/细胞相互作用，测试针对特定优势准种的抗体，将我们的非裔美国患者与白人进行对比。我们将进一步表征假定的HCV受体CD81，以确定其相关蛋白，可能的共受体（项目3）。当我们寻找非裔美国人和白人之间的等位基因变异来解释对治疗反应的差异时，这些数据将与我们的病人联系起来。使用替代病毒模型，我们还将筛选小分子文库，以寻找能够阻断E2/CD81结合的化合物（项目#非裔美国人的反应非常差）。理解这一现象将有助于我们了解为什么目前的治疗方法在所有人群中仍然只是适度成功，将使我们能够预测谁更有可能做出反应，并将为开发更好的治疗方法铺平道路。

The University of Tennessee, Memphis Hepatitis C Cooperative Research Center will use studies of HCV/host interactions to determine why African American patients with HCV respond poorly to standard therapy (interferon and ribavirin). Hepatitis C is common, 1.8% of all Americans, but is even more common among African Americans, and in persons living in poverty. In Memphis, 55% of the population is African American, 34% of whom live below the poverty line. In a previous study, we documented a response rate of only 5% in this population, contrasted with 40% in whites. We propose to systematically characterize the differences between African Americans and whites by allelic variations in cellular ligands/receptors for HCV (Project 1). In Project 2, we will continue to develop an in vitro system for studying HCV, a chimeric VSV virus with the hepatitis C E1 and E2 envelope proteins expressed on its surface. We will use this model to characterize virus/cell interactions, testing antibodies to specific dominant quasispecies, contrasting our African American patients with whites. We will further characterize the putative receptor for HCV, CD81, to define its associated proteins, possible co-receptors (Project 3). These data will interface back to our patients as we search for allelic variations between African Americans and whites to explain the differences in response to therapy. Using the surrogate virus model, we will also screen libraries of small molecules to search for compounds that can block E2/CD81 binding (Project # African American population responds so poorly. Understanding this phenomenon will provide insights into why present day therapy is still only moderately successful in all populations, will allow us to predict who is more likely to respond, and will pave the way to developing better therapy for this emerging health problem.