HEPATITIS C VIRUS COINFECTION IN HIV-1 INFECTED SUBJECTS

描述：(申请人摘要) 丙型肝炎病毒(HCV)合并感染在人类免疫缺陷病毒中很常见 I型(HIV-1)感染者。流行病学数据表明，在HIV-1中 与丙型肝炎病毒重叠感染的患者，丙型肝炎病毒感染更严重，并进展到 艾滋病的传播速度更快。此外，据报道，艾滋病毒感染有助于 据报道，丙型肝炎病毒的母婴传播以及丙型肝炎病毒感染 促进艾滋病毒的母婴传播。我们的总体假设是 丙型肝炎病毒在淋巴样细胞中复制，这一现象是 观察到的HIV-1和丙型肝炎病毒感染之间的相互作用。vbl.使用 链特异性分析，我们已经证明存在丙型肝炎病毒RNA阴性。 链，这是一个病毒复制中介，在多发性肝外 部位，但在淋巴组织中尤其常见。这次感染主要是 定位于单核/巨噬细胞。此外，我们发现病毒序列 在肝外复制部位通常不同于循环和 肝脏衍生的序列。我们的建议旨在进一步描述肝外的特征 HIV-1感染者中的丙型肝炎病毒复制。此外，我们还将分析 外周血单个核细胞中存在丙型肝炎病毒复制 一大群HIV-1阳性母亲的宫颈冲洗液细胞，我们将 将这些数据与丙型肝炎病毒和艾滋病毒-1在儿童中的传播联系起来。至 确定巨噬细胞来源的丙型肝炎病毒株是否与病毒有关 在儿童中传播，我们将分析病毒准种组成 母亲和儿童的血清和PBMCs以及宫颈冲洗液细胞 母亲们。我们还将确定丙型肝炎病毒感染是否呈现抗原 细胞会影响它们的功能。因此，我们将培养树突状细胞 丙型肝炎病毒感染者和非感染者在功能分析中的比较 在试管中。总而言之，我们的研究将进一步表征肝外 丙型肝炎病毒在HIV-1感染者中的复制，并将阐明其在 这两种病毒的母婴传播。

DESCRIPTION: (Applicant's Abstract) Hepatitis C virus (HCV) coinfection is common in human immunodeficiency virus type I (HIV-1) infected subjects. Epidemiological data suggest that in HIV-1 and HCV coinfected patients, HCV infection is more severe and progression to AIDS is more rapid. Furthermore, HIV infection was reported to facilitate mother-to-infant transmission of HCV and also HCV infection was reported to facilitate mother-to-infant transmission of HIV. Our overall hypothesis is that HCV replicates in lymphoid cells and that this phenomenon is responsible for the observed interactions between HIV-1 and HCV infections. Using strand-specific assays, we have demonstrated the presence of HCV RNA negative strand, which is a viral replicative intermediary, in multiple extrahepatic sites, but particularly common in lymphoid tissue. This infection was mainly localized in monocyte/macrophage cells. Moreover, we found that viral sequences at extrahepatic replication sites commonly differ from circulating and liver-derived sequences. Our proposal aims to further characterize extrahepatic HCV replication among HIV-1-infected subjects. Furthermore, we will analyze the presence of HCV replication in peripheral blood mononuclear cells (PBMCs) and cervical lavage cells in a large group of HIV-1-positive mothers and we will correlate these data with transmission of HCV and HIV-1 into children. To determine whether macrophage-derived HCV strains are responsible for viral transmission into children, we will analyze viral quasispecies composition in serum and PBMCs from mothers and children and in cervical lavage cells from mothers. We will also determine whether HCV infection of antigen presenting cells affects their function. Accordingly, we will culture dendritic cells from HCV-infected and uninfected individuals and compare them in functional assays in vitro. In summary, our studies will further characterize extrahepatic replication of HCV in HIV-1 infected subjects and will elucidate its role in mother-to-infant transmission of these two viruses.