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. 2019 Feb 22;6(3):ofz076.
doi: 10.1093/ofid/ofz076. eCollection 2019 Mar.

Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification

Charlotte Hedskog  1 , Bandita Parhy  1 , Silvia Chang  1 , Stefan Zeuzem  2 , Christophe Moreno  3 , Stephen D Shafran  4 , Sergio M Borgia  5 , Tarik Asselah  6 , Laurent Alric  7 , Armand Abergel  8 , Jyh-Jou Chen  9 , Jane Collier  10 , Dharmesh Kapoor  11 , Robert H Hyland  1 , Peter Simmonds  12 , Hongmei Mo  1 , Evguenia S Svarovskaia  1
Affiliations

Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification

Charlotte Hedskog et al. Open Forum Infect Dis. .

Abstract

Background: Hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome.

Methods: Full-genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A, and/or NS5B to HCV genotype (GT) 1-8 reference strains.

Results: A total of 14 653 patients with GT1-6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However, for 19 patients, novel subtypes were identified with <85% homology compared with previously described subtypes. These novel subtypes had the following genotypes: 9 in GT2, 5 in GT4, 2 in GT6, and 1 each in GT1, GT3, and GT5. Despite the presence of polymorphisms at resistance-associated substitution positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12.

Conclusions: Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized.

Keywords: direct-acting antivirals (DAAs); phylogenetic analysis; resistance-associated substitutions (RAS); sofosbuvir; velpatasvir; voxilaprevir.

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Figures

Figure 1.
Figure 1.
Overview of hepatitis C virus (HCV) genotype and subtype assignment of patients enrolled in HCV clinical trials. Abbreviation: GT, genotype.
Figure 2.
Figure 2.
Phylogenetic analysis of genotype 2 and genotype 4 subtypes. Individual maximum likelihood trees were inferred for each genotype, including all previously described confirmed and unassigned subtypes. Previously described subtypes are shown in black, with a corresponding letter for the confirmed subtypes and no letter for the unassigned subtypes. The novel subtypes are shown in red. For genotype 2, 15 confirmed and 8 unassigned subtypes previously described were included. For genotype 4, the 18 confirmed and 10 unassigned subtypes were included in the tree.
Figure 3.
Figure 3.
Phylogenetic analysis of genotype 1, 3, 5, and 6 subtypes. Individual maximum likelihood trees were inferred for each genotype, including all previously described confirmed and unassigned subtypes. Previously described subtypes are shown in black, with a corresponding letter for the confirmed subtypes and no letter for the unassigned subtypes. The novel subtypes are shown in red. For GT1, the 13 confirmed and 7 unassigned subtypes previously described were included. For GT3, the 1 unassigned and 8 confirmed subtypes previously described were included. For GT5, the single confirmed subtype was included. For GT6, the 29 confirmed and 21 unassigned subtypes were included in the tree.
See this image and copyright information in PMC

References

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