Hepatitis C Recombination Incidence and Prevalence

丙型肝炎重组发生率和患病率

• 批准号: 6806549
• 负责人: STUART C RAY
• 金额: $ 16.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806549
• 关键词: genetic recombination; hepatitis C; hepatitis C virus; human tissue; microorganism population study; microorganism resource /registry; polymerase chain reaction; virus genetics

DESCRIPTION (provided by applicant): The purpose of this R21 application is to study HCV recombination, or the exchange of genetic material resulting in hybrid genomes. For HIV-1, recombination was obscure until 1994 but is now recognized as a major mode of genetic diversification, representing an important mechanism for immune evasion and drug resistance. Recently, the first evidence of recombination in HCV was reported in specimens from St. Petersburg, Russia. To date, no other recombinant HCV genomes have been described. Because most studies of HCV genetic sequence have involved small amplicons, whereas identification of a recombinant strain requires examination of multiple genomic regions, we hypothesize that HCV recombination is a more common phenomenon than currently appreciated, and propose initial studies of its frequency and character. We have assembled a large repository of specimens for which genotype has been determined at by sequence analysis of the E1 gene. These specimens have been obtained from infected individuals in 4 U.S. cities where genotypes 1, 2, and 3 predominate, as well as Thailand where genotypes 1, 3, and 6 predominate. We also describe initial investigations of a mixed infection, containing two distinct populations of HCV, which suggest the presence of recombination. Building on years of experience investigating HIV-1 recombination, HCV sequence variation, and the genetic epidemiology of diverse HCV subtypes in Egypt, we propose to examine our repository for evidence of recombination in HCV. The goal of this application is to determine whether genetic recombinant HCV is prevalent, and to performed detailed analysis of recombinant genomes. Specifically, we aim to: (1) identify specimens with discordant genotypes at separate HCV loci, (2) examine specimens containing more than one strain to detect incident recombination, and (3) characterize putative recombinant genomes in detail. Our repository includes well-characterized longitudinally- acquired specimens and we are applying methods for which we have established expertise; therefore, this application has a high likelihood of success. Because the impact of HCV recombination has not yet been determined, R21 funding will provide adequate preliminary data to establish the importance and proper conduct of more extensive investigations.

描述（由申请人提供）：此R21应用的目的是研究HCV重组，或导致杂种基因组的遗传材料的交换。对于HIV-1，直到1994年，重组才变得模糊，但现在被认为是一种主要的遗传多样化方式，代表了免疫逃避和耐药性的重要机制。最近，在俄罗斯圣彼得堡的标本中报道了HCV重组的第一个证据。迄今为止，尚未描述其他重组HCV基因组。由于大多数HCV遗传序列的研究都涉及小扩增子，而重组菌株的鉴定需要检查多个基因组区域，因此我们假设HCV重组比目前所欣赏的更常见的现象，并且提出了对其频率和特征的初步研究。我们组装了一个大型样品存储库，该样本已通过E1基因的序列分析确定了基因型。这些标本是从4个城市中受感染的个体获得的，其中基因型1、2和3占主导地位，以及基因型1、3和6占主导地位的泰国。我们还描述了混合感染的初步研究，其中包含两个不同的HCV种群，这表明存在重组。在研究HIV-1重组，HCV序列变异以及埃及各种HCV亚型的遗传流行病学的多年经验的基础上，我们建议检查我们的存储库以证明HCV重新组合的证据。该应用的目的是确定遗传重组HCV是否普遍存在，并对重组基因组进行了详细的分析。具体而言，我们的目的是：（1）在单独的HCV基因座上识别具有不一致基因型的标本，（2）检查包含多个菌株以检测入射重组的标本，以及（3）详细介绍了推定的重组基因组。我们的存储库包括特定的纵向采集的标本，我们正在应用我们建立专业知识的方法；因此，该应用程序具有很高的成功。由于尚未确定HCV重组的影响，因此R21资金将提供足够的初步数据，以确立更广泛研究的重要性和适当行为。