Geographic distribution of HCV-GT3 subtypes and naturally occurring resistance associated substitutions

Sabrina Bagaglio, Emanuela Messina, Hamid Hasson, Andrea Galli, Caterina Uberti-Foppa, Giulia Morsica

Research output: Contribution to journalArticle

Abstract

Background: Little is known about the frequency or geographic distributions of naturally occurring resistance-associated substitutions (RASs) in the nonstructural protein 5A (NS5A) domain of hepatitis-C virus (HCV) genotype-3 (GT-3) different subtypes. We investigated naturally occurring GT-3 RASs that confer resistance to NS5A inhibitors. Methods: From a publicly accessible database, we retrieved 58 complete GT-3 genomes and an additional 731 worldwide NS5A sequences from patients infected with GT-3 that were naive to direct-acting antiviral treatment. Results: We performed a phylogenetic analysis of NS5A domains in complete HCV genomes to determine more precisely HCV-GT-3 subtypes, based on commonly used target regions (e.g., 50untranslated region and NS5B partial domain). Among 789 NS5A sequences, GT-3nonA subtypes were more prevalent in Asia than in other geographic regions (p < 0.0001). The A30K RAS was detected more frequently in HCV GT-3nonA (84.6%) than in GT-3A subtypes (0.8%), and the amino acid change was polymorphic in isolates from Asia. Conclusions: These results provided information on the accuracy of HCV-3 subtyping with a phylogenetic analysis of the NS5A domain with data from the Los Alamos HCV genome database. This information and the worldwide geographic distribution of RASs according to HCV GT-3 subtypes are crucial steps in meeting the challenges of treating HCV GT-3.

Original languageEnglish
Article number148
JournalViruses
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 2019

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Keywords

  • Geographic distribution
  • HCV genotype 3 subtypes
  • Natural polymorphisms
  • NS5A replication complex inhibitors
  • Resistance-associated substitutions (RASs)

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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