New hepatitis C virus genotype 1 subtype naturally harbouring resistance-associated mutations to NS5A inhibitors

J Gen Virol. 2018 Jan;99(1):97-102. doi: 10.1099/jgv.0.000996. Epub 2017 Dec 14.

Abstract

Hepatitis C virus (HCV) is a highly divergent virus currently classified into seven major genotypes and 86 subtypes (ICTV, June 2017), which can have differing responses to therapy. Accurate genotyping/subtyping using high-resolution HCV subtyping enables confident subtype identification, identifies mixed infections and allows detection of new subtypes. During routine genotyping/subtyping, one sample from an Equatorial Guinea patient could not be classified into any of the subtypes. The complete genomic sequence was compared to reference sequences by phylogenetic and sliding window analysis. Resistance-associated substitutions (RASs) were assessed by deep sequencing. The unclassified HCV genome did not belong to any of the existing genotype 1 (G1) subtypes. Sliding window analysis along the complete genome ruled out recombination phenomena suggesting that it belongs to a new HCV G1 subtype. Two NS5A RASs (L31V+Y93H) were found to be naturally combined in the genome which could limit treatment possibilities in patients infected with this subtype.

Keywords: G1; HCV; RAS; hepatitis C virus; high-resolution HCV subtyping; subtype.

Publication types

  • Case Reports

MeSH terms

  • 2-Naphthylamine
  • Anilides / therapeutic use
  • Antiviral Agents / therapeutic use
  • Benzimidazoles / therapeutic use
  • Carbamates / therapeutic use
  • Drug Resistance, Viral / genetics*
  • Equatorial Guinea
  • Female
  • Fluorenes / therapeutic use
  • Gene Expression
  • Genotype*
  • Hepacivirus / classification
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Imidazoles / therapeutic use
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation*
  • Phylogeny*
  • Proline
  • Pyrrolidines
  • Sequence Analysis, DNA
  • Sulfonamides / therapeutic use
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Valine / analogs & derivatives
  • Viral Nonstructural Proteins / genetics*

Substances

  • Anilides
  • Antiviral Agents
  • Benzimidazoles
  • Carbamates
  • Fluorenes
  • Imidazoles
  • Pyrrolidines
  • Sulfonamides
  • Viral Nonstructural Proteins
  • ledipasvir
  • ombitasvir
  • Uracil
  • Proline
  • 2-Naphthylamine
  • dasabuvir
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir