New HCV isolates SBIR

描述（由申请人提供）：丙型肝炎病毒（HCV）感染是美国慢性肝炎最常见的原因。HCV分为六种不同的基因型之一，每种基因型由各种相关亚型组成。HCV感染患者对抗病毒治疗反应的最重要预测因素之一是病毒基因型。目前，能够在组织培养中自主复制的感染性HCV仅适用于基因型1a、1b和2a。该应用程序旨在创建持续感染HCV新分离株的细胞系，用于药物开发应用。我们的策略是基于一项授权技术的使用，该技术可以提高HCV在组织培养中的复制能力。我们将尝试用含有不同HCV分离株的6个临床样本感染不同的细胞系。如果分离出持续感染新基因型或亚型丙型肝炎病毒的细胞系，可用于抗病毒评估试验，则将取得部分成功。我们是否有能力培养所有使用的HCV临床样本，将表明项目是否成功。如果临床样品中发现的HCV能够在体外繁殖，那么就可以开发出临床样品中耐药性的真正表型测定方法。我们的努力最终将有助于加快丙肝病毒药物的开发，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.