Identification of 2 Novel Subtypes of Hepatitis C Virus Genotype 8 and a Potential New Genotype Successfully Treated With Direct Acting Antivirals.

IF 5 2区医学 Q2 IMMUNOLOGY

Journal of Infectious Diseases Pub Date : 2024-12-16 DOI:10.1093/infdis/jiae253

Jean L Mbisa, Zena Lapp, David F Bibby, Laura T Phillips, Carmen F Manso, Simon Packer, Ruth Simmons, Kathryn Harris, Jaiganesh Mohan, Lalitha Chinnappan, Thomas Leitner, Daniel Bradshaw

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引用次数: 0

Abstract

Background: Hepatitis C virus (HCV) has high genetic diversity and is classified into 8 genotypes and >90 subtypes, with some endemic to specific world regions. This could compromise direct-acting antiviral efficacy and global HCV elimination.

Methods: We characterized HCV subtypes "rare" in the United Kingdom (non-1a/1b/2b/3a/4d) by means of whole-genome sequencing via a national surveillance program. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with International Committee on Taxonomy of Viruses HCV reference sequences.

Results: Two HCV variants were characterized as being closely related to the recently identified genotype (GT) 8, with >85% pairwise genetic distance similarity to GT8 sequences and within the typical intersubtype 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 with other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All 3 were cured with pangenotypic direct-acting antivirals (sofosbuvir-velpatasvir or glecaprevir-pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80K/168E), NS5A (28V/30S/62L/92S/93S) and NS5B (159F).

Conclusions: This study expands our knowledge of HCV diversity by identifying 2 new GT8 subtypes and potentially a new genotype.

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鉴定出两种新型的丙型肝炎病毒基因 8 型亚型和一种潜在的新基因型，并用直接作用抗病毒药物进行了成功治疗。

背景：丙型肝炎病毒（HCV）具有高度遗传多样性，可分为 8 种基因型和 90 多种亚型，其中一些亚型在世界特定地区流行。这可能会影响直接作用抗病毒药物（DAA）的疗效和在全球范围内消除丙型肝炎病毒：方法：我们通过国家监测计划进行全基因组测序，确定了英国 "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，对未确定基因型的样本进行基因分析，以确定其基因型：两个HCV变异体的特征是与最近确定的基因型8（GT8）密切相关，与GT8序列的成对遗传距离相似度大于85%，且在典型的亚型间遗传距离范围内。受这些变体感染的人都是来自巴基斯坦和印度的英国居民。与此相反，第三个变体仅在基因组的 6% 范围内被确定为与 GT6 更为相似，并且是从一名原籍圭亚那的英国居民身上分离出来的。尽管在NS3（80 K/168E）、NS5A（28 V/30S/62L/92S/93S）和NS5B（159F）中存在耐药多态性，但这三个变异株都能通过泛基因型DAAs（索非布韦+韦帕他韦或格列卡普韦+皮布伦达韦）治愈：这项研究通过鉴定两种新的 GT8 亚型和一种潜在的新基因型，扩展了我们对 HCV 多样性的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infectious Diseases 医学-传染病学

CiteScore

13.50

自引率

3.10%

发文量

449

审稿时长

2-4 weeks

期刊介绍： Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.