MOLECULAR BIOLOGY OF HEPATITIS C VIRUS

丙型肝炎病毒的分子生物学

• 批准号: 3790817
• 负责人: R H MILLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790817
• 关键词: blood transfusion; communicable disease diagnosis; genetic strain; genome; hepatitis C virus; liver disorder diagnosis; microorganism immunology; molecular pathology; nucleic acid sequence; polymerase chain reaction; protein sequence; serology /serodiagnosis; virus cytopathogenic effect; virus genetics; virus infection mechanism; virus load; virus protein; virus replication

Hepatitis C virus (HCV) is an important human pathogen that is strongly associated with transfusion related non-A, non-B (NANB) hepatitis. Amplification of HCV RNA sequences by reverse transcription and polymerase chain reaction (cDNA PCR) is the only practical method currently available to demonstrate viremia in patients with HCV infection. However, genetic heterogeneity among different HCV strains results in false negative results in cDNA PCR assays because of primer and template mismatch. HCV accounts for up to 25% of community-acquired hepatitis and over 90% of transfusion- associated hepatitis in the United States. The recent cloning and sequencing of the genome of HCV led to the development of specific serologic tests for antibody to HCV (anti-HCV) that utilized recombinant- derived viral antigens. These tests have been useful for diagnostic and screening purposes but they shed little light on immunity to HCV, in part because currently available antigens are expressed from parts of the HCV genome that encode nonstructural or internal structural proteins. Furthermore, the finding of genetic heterogeneity of the HCV genome, especially in the gene encoding the envelope proteins, suggests that there may be heterogeneity of viral envelope proteins similar to that seen in human immunodeficiency viruses. Such a finding would bode ill for attempts at vaccine development. The objectives of this project are to: (1) identify primer sets that have a low false negative rate in a cDNA PCR assay; (2) determine the nucleotide sequence of diverse HCV genomes; and (3) analyze whether infection of primates with HCV induces protective immunity.

丙型肝炎病毒（HCV）是一种重要的人类病原体，具有很强的传染性。 与输血相关的非甲非乙型 (NANB) 肝炎有关。 通过逆转录和聚合酶扩增 HCV RNA 序列 链式反应（cDNA PCR）是目前唯一实用的方法 证明 HCV 感染患者的病毒血症。 然而，遗传 不同HCV毒株之间的异质性导致假阴性结果 在 cDNA PCR 测定中，由于引物和模板不匹配。 丙肝病毒账户 高达 25% 的社区获得性肝炎和超过 90% 的输血 - 在美国有相关肝炎。 最近的克隆和 HCV 基因组测序导致了特定的开发 利用重组体进行 HCV 抗体（抗 HCV）血清学检测 衍生的病毒抗原。 这些测试对于诊断和诊断非常有用 筛查目的，但它们在一定程度上对丙肝病毒免疫力的了解很少 因为目前可用的抗原是由 HCV 的部分表达的 编码非结构或内部结构蛋白的基​​因组。 此外，HCV基因组遗传异质性的发现， 特别是在编码包膜蛋白的基因中，表明存在 可能是病毒包膜蛋白的异质性，类似于在 人类免疫缺陷病毒。 这样的发现对于尝试来说是不吉利的 在疫苗开发方面。 该项目的目标是：（1） 识别 cDNA PCR 中假阴性率较低的引物组 化验； (2)确定不同HCV基因组的核苷酸序列；和 (3)分析灵长类动物感染HCV是否会产生保护作用 免疫。