NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Naïve Patients with Chronic Hepatitis C

Deborah D'Aliberti, Irene Cacciola, Cristina Musolino, Giuseppina Raffa, Roberto Filomia, Angela Alibrandi, Salvatore Benfatto, Concetta Beninati, Carlo Saitta, Domenico Giosa, Orazio Romeo, Giovanni Raimondo, Teresa Pollicino

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Hepatitis C virus (HCV) NS3 resistance-associated substitutions (RASs) reduce HCV susceptibility to protease inhibitors. Little is known about NS3 RASs in viral isolates from the liver of chronic hepatitis C (CHC) patients infected with HCV genotype-1a (G1a).

AIM: The objective of this work was to study NS3 variability in isolates from the serum and liver of HCV-G1a-infected patients naïve to direct-acting antivirals (DAAs).

METHODS: NS3 variability of HCV-G1a isolates from the serum and liver of 11 naïve CHC patients, and from sera of an additional 20 naïve CHC patients, was investigated by next-generation sequencing.

RESULTS: At a cutoff of 1%, NS3 RASs were detected in all the samples examined. At a cutoff of 15%, they were found in 54.5% (6/11) and 27.3% (3/11) of the paired liver and serum samples, respectively, and in 22.5% (7/31) of the overall serum samples examined. Twenty-six out of thirty-one (84%) patients showed NS3 variants with multiple RASs. Phylogenetic analysis showed that NS3 sequences clustered within 2 clades, with 10/31 (32.2%) patients infected by clade I, 15/31 (48.8%) by clade II, and 6/31 (19.3%) by both clades.

CONCLUSIONS: Though the number of patients examined was limited, NS3 variants with RASs appear to be major components of both intrahepatic and circulating viral quasispecies populations in DAA-naïve patients.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalIntervirology
Volume61
Issue number1
DOIs
Publication statusPublished - Aug 1 2018

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Keywords

  • Adult
  • Amino Acid Substitution
  • Antiviral Agents/pharmacology
  • Drug Resistance, Viral
  • Female
  • Genetic Variation
  • Genotype
  • Hepacivirus/enzymology
  • Hepatitis C, Chronic/epidemiology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Italy/epidemiology
  • Liver/virology
  • Male
  • Middle Aged
  • Phylogeny
  • Protease Inhibitors/pharmacology
  • Serum/virology
  • Viral Nonstructural Proteins/genetics

Cite this

D'Aliberti, D., Cacciola, I., Musolino, C., Raffa, G., Filomia, R., Alibrandi, A., Benfatto, S., Beninati, C., Saitta, C., Giosa, D., Romeo, O., Raimondo, G., & Pollicino, T. (2018). NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Naïve Patients with Chronic Hepatitis C. Intervirology, 61(1), 1-8. https://doi.org/10.1159/000489307