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

doi:10.1159/000489307

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

IRCCS Centro Neurolesi "Bonino Pulejo"

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1-8
Number of pages	8
Journal	Intervirology
Volume	61
Issue number	1
DOIs	https://doi.org/10.1159/000489307
Publication status	Published - Aug 1 2018

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

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10.1159/000489307

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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

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, vol. 61, no. 1, pp. 1-8. https://doi.org/10.1159/000489307

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title = "NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Na{\"i}ve Patients with Chronic Hepatitis C",

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 na{\"i}ve to direct-acting antivirals (DAAs).METHODS: NS3 variability of HCV-G1a isolates from the serum and liver of 11 na{\"i}ve CHC patients, and from sera of an additional 20 na{\"i}ve 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-na{\"i}ve patients.",

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",

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

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doi = "10.1159/000489307",

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T1 - NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Naïve Patients with Chronic Hepatitis C

AU - D'Aliberti, Deborah

AU - Cacciola, Irene

AU - Musolino, Cristina

AU - Raffa, Giuseppina

AU - Filomia, Roberto

AU - Alibrandi, Angela

AU - Benfatto, Salvatore

AU - Beninati, Concetta

AU - Saitta, Carlo

AU - Giosa, Domenico

AU - Romeo, Orazio

AU - Raimondo, Giovanni

AU - Pollicino, Teresa

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

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KW - Amino Acid Substitution

KW - Antiviral Agents/pharmacology

KW - Drug Resistance, Viral

KW - Female

KW - Genetic Variation

KW - Genotype

KW - Hepacivirus/enzymology

KW - Hepatitis C, Chronic/epidemiology

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Italy/epidemiology

KW - Liver/virology

KW - Male

KW - Middle Aged

KW - Phylogeny

KW - Protease Inhibitors/pharmacology

KW - Serum/virology

KW - Viral Nonstructural Proteins/genetics

U2 - 10.1159/000489307

DO - 10.1159/000489307

M3 - Article

C2 - 30021203

SN - 0300-5526

VL - 61

SP - 1

EP - 8

JO - Intervirology

JF - Intervirology

IS - 1

ER -

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

Abstract

Keywords

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