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

使用超深度测序分析 HIV/HCV 性传播对

• 批准号: 8330105
• 负责人: DAVID L WYLES
• 金额: $ 23.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330105
• 关键词: Acute; Anatomy; Blood; Cause of Death; Characteristics; Chronic Hepatitis C; Clinical; Data; Detection; Disease; Disease Outbreaks; Enrollment; Environment; Epidemiology; Event; Evolution; Generations; Genital system; Genotype; Goals; Grant; HIV; HIV Seropositivity; Hepatitis C; Hepatitis C Transmission; Hepatitis C virus; High Prevalence; Infection; Lead; Leukocytes; Life Cycle Stages; Link; Liquid substance; Liver; Liver diseases; Methods; Peripheral Blood Mononuclear Cell; Persons; Phylogenetic Analysis; Plasma; Plasma Cells; Play; Population; Prevention; RNA; RNA-Directed RNA Polymerase; Recurrence; Relative (related person); Research; Role; Sampling; Seminal Plasma; Seminal fluid; Sexual Transmission; Sexually Transmitted Diseases; Source; Staging; Untranslated Regions; Variant; Vertical Disease Transmission; Viral; Virus; Virus Replication; base; epidemiologic data; improved; information gathering; insight; interest; liver transplantation; men who have sex with men; pressure; prevent; sex; transmission process; virus host interaction

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.

描述（由申请人提供）：该赠款旨在通过研究五个HCV性传播对来增强我们对丙型肝炎病毒（HCV）性传播的理解。数据表明，HCV可以在包括肝脏，白细胞以及生殖道（1-3）的几个解剖区室中复制。此外，在这些不同隔室中复制的病毒可以以其序列的微小差异为特征。该研究的主要目的是确定在传输伙伴中，通过确定其序列特征来确定在受体中建立感染的HCV。在鉴定出可能通过性别获得HCV的传播对后，将从源伴侣中收集可能参与传播的体液样品，包括精液和血液。还将从获得HCV感染的对受试者中收集血液。从这些流体中分离出HCV后，我们将使用大量平行的测序方法来生成各个区室中HCV的详细序列签名。然后，我们将在传输和受体伴侣之间比较这些序列特征，以确定感染伴侣可能起源于发射机的病毒。该研究的第二个目的是确定与艾滋病毒共同感染的人和单独拥有HCV的人之间是否存在差异和分布之间的差异。为了实现这一目标，将招募另外5名受试者，以便我们可以分析5 HCV和5 HCV/HIV长期感染的受试者，这些受试者要么传播HCV或可能是HCV发射器。 公共卫生相关性：最近在与男性发生性关系的艾滋病毒阳性男性中认可了性传播的HCV感染的爆发（4）。考虑到HIV共感染的HCV的高患病率和加速临床过程，该组特别感兴趣（5）。从这些研究中收集的信息应增加我们对HCV复制和传播的理解，并有可能导致改进的防止传播的策略。