Analysis of HIV/HCV Sexual Transmission Pairs Using Ultra-Deep Sequencing

描述(申请人提供)：这项资助旨在通过研究五对丙型肝炎病毒的性传播来增加我们对丙型肝炎病毒(丙型肝炎病毒)性传播的了解。数据表明，丙型肝炎病毒可以在几个解剖间隔内复制，包括肝脏、白细胞和生殖道内(1-3)。此外，在这些不同的间隔中复制的病毒可以通过它们的序列的微小差异来表征。这项研究的主要目的是通过确定其序列特征来确定在接受者中确定感染的丙型肝炎病毒来自于传播伙伴的哪里。在确定可能通过性行为感染丙型肝炎病毒的传播对后，将从来源伴侣那里收集可能涉及传播的体液样本，包括精液和血液。还将从感染丙型肝炎病毒的受试者身上采集血液。在从这些液体中分离出丙型肝炎病毒后，我们将使用大规模并行测序方法来生成各个隔间中丙型肝炎病毒的详细序列签名。然后，我们将比较发送伙伴和接收伙伴之间的这些序列签名，以确定感染伙伴的病毒可能来自于发送方。这项研究的第二个目的是确定合并感染艾滋病毒的人和单独感染丙型肝炎病毒的人之间是否存在丙型肝炎病毒序列和分布的差异。为了实现这一点，我们将额外招募5名受试者，以便我们能够分析5名丙型肝炎病毒和5名丙型肝炎病毒/艾滋病毒慢性感染者，他们要么是丙型肝炎病毒的传播者，要么可能是丙型肝炎病毒的传播者。

DESCRIPTION (provided by applicant): This grant seeks to increase our understanding of Hepatitis C virus (HCV) sexual transmission by studying five HCV sexual transmission pairs. Data suggests that HCV can replicate in several anatomic compartments including the liver, white blood cells, and within the genital tract (1-3). Furthermore, viruses replicating in these different compartments can be characterized by small differences in their sequences. The primary aim of the research is to determine where in the transmitting partner the HCV that established infection in the recipient came from by determining their sequence characteristics. Following identification of transmission pairs where HCV was likely acquired via sex, samples of bodily fluids that may be involved in transmission will be collected from the source partner including semen and blood. Blood will also be collected from the subject in the pair who acquired HCV infection. Following isolation of HCV from these fluids we will use massively parallel sequencing methods to generate a detailed sequence signature for the HCV in the various compartments. We will then compare these sequence signatures between the transmitting and recipient partners to determine where the virus that infected the partner likely originated in the transmitter. A second aim of the research is to determine whether difference exist in HCV sequences and distribution between persons who are co-infected with HIV and those who have HCV alone. To accomplish this an additional 5 subjects will be enrolled so that we can analyze 5 HCV and 5 HCV/HIV chronically infected subjects who either transmitted HCV or would be possible HCV transmitters.