New HCV isolates SBIR

描述(申请人提供)：感染丙型肝炎病毒(丙型肝炎病毒)是美国慢性肝炎最常见的原因。丙型肝炎病毒分为六种不同的基因类型之一，每种基因类型都由不同的相关亚型组成。预测患者对丙型肝炎病毒感染的抗病毒治疗反应的最重要的预测因素之一是病毒基因型。目前，在组织培养中能够自主复制的感染性丙型肝炎病毒只适用于1a、1b和2a基因型。这项应用旨在创造持续感染新的丙型肝炎病毒分离株的细胞系，用于药物开发应用。我们的战略是基于使用一种许可的技术，在组织培养中增加丙型肝炎病毒的复制能力。我们将利用这项技术，尝试用含有不同丙型肝炎病毒分离株的6份临床样本感染不同的细胞系。部分成功将被定义为分离出持续感染新的丙型肝炎病毒基因或亚型的细胞系，可用于抗病毒评估分析。整个项目的成功将通过我们培养所有使用的丙型肝炎病毒临床样本的能力来表明。如果临床标本中发现的丙型肝炎病毒能够在体外繁殖，那么临床标本中真实的耐药表型分析就有可能建立起来。我们的努力最终将有助于加快丙型肝炎病毒药物的开发，从而改善公共卫生。 丙型肝炎病毒(丙型肝炎病毒)感染患者对抗病毒治疗的反应最重要的预测指标之一是病毒基因型。目前，只有三种可以在组织培养中复制的丙型肝炎病毒分离株可用。这一SBIR应用程序旨在创建持续感染新的丙型肝炎病毒临床分离株的细胞系。如果临床标本中发现的丙型肝炎病毒能够在体外繁殖，那么在药物开发过程中可以使用其他病毒基因型，并可以建立临床标本中真实的耐药表型分析。这将有助于加快丙型肝炎病毒药物的开发，从而改善公共卫生。

DESCRIPTION (provided by applicant): Infection with the hepatitis C virus (HCV) is the most common cause of chronic hepatitis in the United States. HCV is classified into one of six different genotypes, each composed of a variety of related subtypes. One of the most important predictors of the response of patients to antiviral therapy for HCV infection is viral genotype. Currently, infectious HCV that are able to replicate autonomously in tissue culture are available only for genotypes 1a, 1b and 2a. This application aims to create cell lines that are persistently-infected with new isolates of HCV for drug development applications. Our strategy is based on the use of a licensed technology that increases the replicative ability of HCV in tissue culture. We will try to infect various cell lines with six clinical samples containing various isolates of HCV by using this technology. Partial success will be defined as the isolation of a cell line persistently-infected with a new genotype or subtype of HCV that can be used for antiviral evaluation assays. Complete project success will be indicated by our ability to culture all of the clinical samples of HCV utilized. If the HCV found in clinical samples can be propagated in vitro, then a true phenotypic assay of drug resistance in clinical samples could be developed. Our efforts will ultimately help expedite drug development for HCV, leading to improvements in Public Health. One of the most important predictors of the response of patients to antiviral therapy for hepatitis C virus (HCV) infection is viral genotype. Currently, only three isolates of HCV that can replicate in tissue culture are available. This SBIR application aims to create cell lines that are persistently- infected with new clinical isolates of HCV. If the HCV found in clinical samples can be propagated in vitro, then other viral genotypes could be used during drug development and a true phenotypic assay of drug resistance in clinical samples could be developed. This would help expedite drug development for HCV, leading to improvements in Public Health.