HEPATITIS C VIRUS COINFECTION IN HIV-1 INFECTED SUBJECTS

描述：（申请人摘要） 丙型肝炎病毒（HCV）合并感染是人类免疫缺陷病毒（HIV）常见的并发症 I型（HIV-1）感染的受试者。流行病学数据表明，在HIV-1中， 与HCV合并感染患者相比，HCV感染更严重，并进展为 艾滋病传播更快。此外，据报道，艾滋病毒感染 据报道，母婴传播HCV和HCV感染， 促进艾滋病毒的母婴传播。我们的总体假设是 HCV在淋巴细胞中复制，这种现象是导致 观察到的HIV-1和HCV感染之间的相互作用。使用 链特异性检测，我们已经证明存在HCV RNA阴性 股，这是一个病毒复制的中介，在多个肝外 部位，但在淋巴组织中特别常见。这种感染主要是 位于单核细胞/巨噬细胞中。此外，我们发现病毒序列 在肝外复制位点通常不同于循环， 肝源性序列我们的建议旨在进一步描述肝外 HIV-1感染者中的HCV复制。此外，我们将分析 外周血单核细胞（PBMC）中存在HCV复制， 宫颈灌洗液细胞在一大群HIV-1阳性的母亲，我们将 将这些数据与HCV和HIV-1向儿童的传播相关联。到 确定巨噬细胞来源的HCV毒株是否负责病毒 传播到儿童，我们将分析病毒准种组成， 来自母亲和儿童的血清和PBMC以及来自母亲和儿童的宫颈灌洗液细胞中的 妈妈们我们还将确定HCV感染是否与抗原提呈有关， 细胞影响其功能。因此，我们将培养树突状细胞， HCV感染者和未感染者，并在功能测定中比较它们 体外总之，我们的研究将进一步描述肝外 HCV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.