Background Hepatitis C virus (HCV) has a high genetic diversity and is classified into 8 genotypes and over 90 subtypes with some endemic to specific world regions. This could compromise direct-acting antiviral (DAA) efficacy and global HCV elimination. Methods We characterised HCV subtypes ‘rare’ to the UK (non-1a/1b/2b/3a/4d) by whole genome sequencing via a national surveillance programme. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with ICTV HCV reference sequences. Results Two HCV variants were characterised as being closely related to the recently identified genotype 8 (GT8), with >85% pairwise genetic distance similarity to GT8 sequences and within the typical inter-subtype genetic distance range. The individuals infected by the variants were UK residents originally from Pakistan and India. In contrast, a third variant was only confidently identified to be more similar to GT6 compared to other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All three were cured with pangenotypic DAAs (Sofosbuvir + Velpatasvir or Glecaprevir + Pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80 K/168E), NS5A (28 V/30S/62L/92S/93S) and NS5B (159F). Conclusions This study expands our knowledge of HCV diversity by identifying two new GT8 subtypes and potentially a new genotype.

中文翻译：

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鉴定出丙型肝炎病毒基因型 8 的两种新亚型以及直接作用抗病毒药物成功治疗的潜在新基因型

背景丙型肝炎病毒（HCV）具有高度遗传多样性，分为8个基因型和90多个亚型，其中一些是世界特定地区流行的。这可能会损害直接作用抗病毒 (DAA) 功效和全球丙肝病毒消除。方法 我们通过国家监测计划通过全基因组测序来表征英国“罕见”的 HCV 亚型（非 1a/1b/2b/3a/4d）。通过与 ICTV HCV 参考序列进行比较，进行遗传分析以确定具有未解析基因型的样本的基因型。结果 两种HCV变体被表征为与最近鉴定的基因型8(GT8)密切相关，与GT8序列具有＞85％的成对遗传距离相似性并且在典型的亚型间遗传距离范围内。感染该变种的人是来自巴基斯坦和印度的英国居民。相比之下，第三个变体仅被确定为与 GT6 相比在 6% 的基因组中与其他基因型更相似，并且是从来自圭亚那的英国居民中分离出来的。尽管 NS3 (80 K/168E)、NS5A (28 V/30S/62L/92S/93S) 和 NS5B (159F) 中存在耐药多态性，但这三名患者均通过全基因型 DAA（索磷布韦 + Velpatasvir 或 Glecaprevir + Pibrentasvir）治愈。结论 这项研究通过鉴定两种新的 GT8 亚型和潜在的新基因型，扩展了我们对 HCV 多样性的认识。