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

描述（由申请人提供）：该补助金旨在通过研究五对丙型肝炎病毒（HCV）性传播来增加我们对HCV性传播的理解。数据表明，HCV可以在几个解剖隔室中复制，包括肝脏、白色血细胞和生殖道内（1-3）。此外，在这些不同区室中复制的病毒可以通过它们的序列的微小差异来表征。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建立感染的HCV在传播伙伴中的位置。在确定可能通过性行为获得HCV的传播对后，将从源伴侣处收集可能参与传播的体液样本，包括精液和血液。还将从获得HCV感染的受试者对中采集血液。从这些液体中分离HCV后，我们将使用大规模平行测序方法来生成各个隔室中HCV的详细序列特征。然后，我们将比较发送方和接收方之间的这些序列特征，以确定感染伴侣的病毒可能来自发送方的何处。本研究的第二个目的是确定是否存在差异，在HCV的序列和分布之间的人谁是共同感染艾滋病毒和那些谁只有HCV。为了实现这一目标，将额外入组5例受试者，以便我们可以分析5例HCV和5例HCV/HIV慢性感染受试者，这些受试者传播HCV或可能是HCV传播者。 公共卫生相关性：最近在与男性发生性关系的HIV阳性男性中发现了性传播HCV感染的爆发（4）。考虑到在HIV合并感染的情况下HCV的高患病率和加速的临床病程，这一组特别令人感兴趣（5）。从这些研究中收集的信息应该会增加我们对丙型肝炎病毒复制和传播的了解，并可能导致预防传播策略的改进。

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. PUBLIC HEALTH RELEVANCE: An outbreak of sexually transmitted HCV infection has recently been recognized among HIV positive men who have sex with men (4). This group is of particular interest given the high prevalence and accelerated clinical course of HCV in the setting of HIV co-infection (5). The information gathered from these studies should increase our understanding of HCV replication and transmission and could potentially lead to improved strategies to prevent transmission.