Identification of a Novel Hepatitis C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 Genotypes

Identification of a Novel Hepatitis C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 Genotypes
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DOI:
10.1093/infdis/jiy401
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发表时间:
2018-12-01
影响因子:
6.4
通讯作者:
Shafran, Stephen D.
Shafran, Stephen D.
中科院分区:
医学2区
文献类型:
--
作者:
Borgia, Sergio M.;Hedskog, Charlotte;Shafran, Stephen D.

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背景丙型肝炎病毒(HCV)具有很大的遗传多样性,分为7个基因型(GT),不同的地理流行。直到最近开发的泛基因型直接作用的抗病毒治疗方案,HCV GT的测定是必要的,以告知最佳的治疗。用标准的商业基因分型方法对未分辨GT的血浆样本进行HCV全基因组测序,并进行系统发育分析以分配GT。4名患者,以前归类为GT 5的利帕或雅培实时聚合酶链反应检测,被确定为感染了一种新的HCV GT。这种新的HCV GT,GT 8,是从遗传上不同于以前确定的HCV GT 1 -7与> 30%的核苷酸序列的分歧,以建立HCV亚型。所有4例患者均来自印度旁遮普,但现居住在加拿大,在流行病学上无关联。尽管所有4例患者的GT 8病毒内存在基线耐药相关置换(NS 3:V36 L,Q80 K/R; NS 5A:Q30 S,Y 93 S),但所有患者均获得了持续的病毒学应答; 2例接受索非布韦/维帕他韦/伏西瑞韦治疗8周,1例接受索非布韦/雷迪帕韦加利巴韦林治疗24周,1例接受索非布韦加达卡他韦治疗12周。一种新的HCV GT 8的发现证实了这种新发现的谱系在人群中的传播。
Background. Hepatitis C virus (HCV) exhibits great genetic diversity and is classified into 7 genotypes (GTs), with varied geographic prevalence. Until the recent development of pangenotypic direct-acting antiviral regimens, the determination of HCV GT was necessary to inform optimal treatment.Methods. Plasma samples with unresolved GT using standard commercial genotyping methods were subjected to HCV full-genome sequencing, and phylogenetic analysis was performed to assign GT.Results. Four patients, previously classified as GT5 by LiPA or Abbott RealTime polymerase chain reaction assays, were identified as infected with a novel HCV GT. This novel HCV GT, GT8, is genetically distinct from previously identified HCV GT1-7 with > 30% nucleotide sequence divergence to the established HCV subtypes. All 4 patients were originally from Punjab, India, but now reside in Canada and are epidemiologically unlinked. Despite presence of baseline resistance-associated substitutions within the GT8 virus of all 4 patients (NS3: V36L, Q80K/R; NS5A: Q30S, Y93S), all patients achieved a sustained virologic response; 2 treated with sofosbuvir/velpatasvir/voxilaprevir for 8 weeks, 1 with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and 1 with sofosbuvir plus daclatasvir for 12 weeks.Conclusions. The discovery of a novel HCV GT8 confirms the circulation of this newly identified lineage in the human population.