Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
Department of Innate Immunity, ICMR-National Institute for Research in Reproductive and Child Health, Mumbai 400012, India.
Viruses. 2022 Apr 30;14(5):944. doi: 10.3390/v14050944.
Hepatitis C Virus (HCV) genotype (GT) 6 demonstrates maximum genomic diversity out of all the known genotypes of HCV, attributable to its inherent intra-genotype and inter-genotype recombination property. This is the most common genotype seen in HCV/HIV co-infected cases. HIV/HCV co-infection is linked with increased genetic diversity in HCV structural genes. The detailed information on the distribution of HCV GT6, its subtypes, and resistance to currently available antiviral drugs is limited in the Indian subcontinent. Therefore, in this single-center retrospective cross-sectional study, we aimed to map the occurrence of HCV GT6, its subtypes and resistance-associated substitution (RAS), and its correlation with antiviral treatment response in HCV-infected patients. From a cohort of 2052 HCV-infected patients, the overall prevalence of GT6 was 2.5% ( = 53), with a maximum of 81.1% ( = 43) seen in HCV/HIV co-infected patients. Nine different subtypes, 6a, 6b, 6f, 6i, 6n, 6u, 6v, 6w, and 6xa, were detected in the Indian population for the first time, with a predominance of 6xa (41.5%), a rare subtype, followed by 6n (39.6%). The phylogenetic analysis by the neighbor-joining method revealed three prominent viral clades, 6v, 6n, and 6xa-6u. The baseline (before treatment initiation) plasma samples of all GT6-infected patients were retrieved from -80 °C and a part of the NS5a and NS5b region of the viral genome was analyzed for the presence of RAS. No RASs were seen in the NS5b region, while in two patients (3.7%) RASs were seen at baseline in the NS5a region of the virus. Sustained viral response (SVR) was attained in 81% ( = 43) of patients. No difference in GT6 subtype distribution or occurrence of RAS was seen between mono-infected HCV and HIV/HCV co-infected cases. Our study revealed that RAS at baseline did not influence the attainment of SVR and the currently available antiviral therapy is effective against GT6 mono-infected and HIV/HCV co-infected patients.
丙型肝炎病毒（HCV）基因型（GT）6 在所有已知 HCV 基因型中表现出最大的基因组多样性，这归因于其内在的基因型内和基因型间重组特性。这是 HCV/HIV 合并感染病例中最常见的基因型。HIV/HCV 合并感染与 HCV 结构基因的遗传多样性增加有关。在印度次大陆，关于 HCV GT6 的分布、其亚型以及对现有抗病毒药物的耐药性的详细信息有限。因此，在这项单中心回顾性横断面研究中，我们旨在描绘 HCV GT6 的发生情况，及其亚型和耐药相关取代（RAS），以及其与 HCV 感染患者抗病毒治疗反应的相关性。在 2052 例 HCV 感染患者的队列中，GT6 的总流行率为 2.5%（=53），在 HCV/HIV 合并感染患者中最高达 81.1%（=43）。在印度人群中首次检测到 9 种不同的亚型，包括 6a、6b、6f、6i、6n、6u、6v、6w 和 6xa，其中以 6xa（41.5%）为主导，这是一种罕见的亚型，其次是 6n（39.6%）。通过邻接法进行的系统进化分析显示了三个主要的病毒分支，即 6v、6n 和 6xa-6u。从-80°C 检索了所有 GT6 感染患者的基线（治疗开始前）血浆样本，并分析了病毒基因组的 NS5a 和 NS5b 区部分区域中 RAS 的存在情况。在 NS5b 区未发现 RAS，而在两名患者（3.7%）的病毒 NS5a 区中，基线时发现了 RAS。81%（=43）的患者获得了持续病毒学应答（SVR）。在单感染 HCV 和 HIV/HCV 合并感染病例中，GT6 亚型分布或 RAS 的发生无差异。我们的研究表明，基线时的 RAS 并不影响 SVR 的获得，目前的抗病毒治疗对 GT6 单感染和 HIV/HCV 合并感染患者有效。
