首页> 外文OA文献 >NS3 protease polymorphism and natural resistance to protease inhibitors in French patients infected with HCV genotypes 1–5
【2h】

NS3 protease polymorphism and natural resistance to protease inhibitors in French patients infected with HCV genotypes 1–5

机译:Ns3蛋白酶多态性和感染HCV基因型的法国患者对蛋白酶抑制剂的天然抗性1-5

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Background: Resistant HCV populations may pre-exist in patients before NS3 protease inhibitor therapy and would likely be selected under specific antiviral pressure. The higher prevalence and lower rate of response to treatment associated with HCV genotype 1 infections has led to drug discovery efforts being focused primarily on enzymes produced by this genotype. Protease inhibitors may also be useful for non-genotype-1-infected patients, notably for non-responders.Methods: We investigated the prevalence of dominant resistance mutations and polymorphism in 298 HCV protease-inhibitor-naive patients infected with HCV genotypes 1, 2, 3, 4 or 5. Genotype-specific NS3 primers were designed to amplify and sequence the NS3 protease gene. Results: None of the 233 analysed sequences contained major telaprevir (TVR) or boceprevir (BOC) resistance mutations (R155K/T/M, A156S/V/T and V170A). Some substitutions (V36L, T54S, Q80K/R, D168Q and V170T) linked to low or moderate decreases in HCV sensitivity to protease inhibitors were prevalent according to genotype (between 2% and 100%). Other than genotype signature mutations at positions 36, 80 and 168, the most frequent substitution was T54S (4 genotype 1 and 2 genotype 4 sequences). All genotype 2–5 sequences had the non-genotype-1 signature V36L mutation known to confer low-level resistance to both TVR and BOC. Conclusions: We have developed an HCV protease NS3 inhibitor resistance genotyping tool suitable for use with HCV genotypes 1–5. Polymorphism data is valuable for interpreting genotypic resistance profiles in cases of failure of anti-HCV NS3 protease treatment.
机译:背景:耐药的HCV人群可能在NS3蛋白酶抑制剂治疗之前就已经存在于患者中,并且可能会在特定的抗病毒压力下进行选择。与HCV基因型1型感染相关的治疗的较高患病率和较低的响应率已导致药物发现工作主要集中在由该基因型产生的酶上。蛋白酶抑制剂也可能对非基因型1感染的患者有用,特别是对无反应者。方法:我们调查了298例HCV蛋白酶抑制剂初免患者感染HCV基因型1、2的显性耐药突变和多态性的患病率。 ,3、4或5。设计基因型特异性NS3引物来扩增和测序NS3蛋白酶基因。结果:233个分析序列均未包含主要的特拉普韦(TVR)或博西普韦(BOC)抗性突变(R155K / T / M,A156S / V / T和V170A)。根据基因型(在2%至100%之间),一些与HCV对蛋白酶抑制剂敏感性低或中等降低相关的取代(V36L,T54S,Q80K / R,D168Q和V170T)普遍存在。除了在位置36、80和168的基因型签名突变外,最常见的替换是T54S(4个基因型1和2个基因型4序列)。所有2-5型基因序列均具有非1型特征性V36L突变,已知可对TVR和BOC产生低水平抗性。结论:我们已经开发了适用于HCV基因型1-5的HCV蛋白酶NS3抑制剂抗性基因分型工具。在抗HCV NS3蛋白酶治疗失败的情况下,多态性数据对于解释基因型耐药谱非常有价值。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号