Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients
Highlights • Identification of a duplicated V3-NS5A domain in HCV1b strains infected French patients. • The prevalence of this strain in our multicenter cohort was 3.05%. • The duplication was present in the entire quasispecies at any time of the infection. • The duplication prevalence increased wit...
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| Published in: | Journal of clinical virology Vol. 69; pp. 203 - 209 |
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| Abstract | Highlights • Identification of a duplicated V3-NS5A domain in HCV1b strains infected French patients. • The prevalence of this strain in our multicenter cohort was 3.05%. • The duplication was present in the entire quasispecies at any time of the infection. • The duplication prevalence increased with the liver disease severity. |
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| AbstractList | Background The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. Objectives In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. Study Design We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. Results We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e-5, thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p =0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). Conclusions We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis. Highlights • Identification of a duplicated V3-NS5A domain in HCV1b strains infected French patients. • The prevalence of this strain in our multicenter cohort was 3.05%. • The duplication was present in the entire quasispecies at any time of the infection. • The duplication prevalence increased with the liver disease severity. •Identification of a duplicated V3-NS5A domain in HCV1b strains infected French patients.•The prevalence of this strain in our multicenter cohort was 3.05%.•The duplication was present in the entire quasispecies at any time of the infection.•The duplication prevalence increased with the liver disease severity. The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e−5, thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis. Background The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. Objectives In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. Study Design We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. Results We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e-5, thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). Conclusions We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5), thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis. |
| Author | André, P Bouthry, E Rosenberg, A.R Saoudin, H Pawlotsky, J.M Le Guillou-Guillemette, H Gaudy-Graffin, C André-Garnier, E Petsaris, O Stoll-Keller, F Henquell, C Lagathu, G Lunel-Fabiani, F Trimoulet, P Bertrais, S Izopet, J Veillon, P Minjolle-Cha, S Baazia, Y Bour, J.B Bettinger, D Payan, C Vallet, S Ducancelle, A Alain, S Thibault, V Larrat, S Lemaire, C Pivert, A Pozzetto, B Signori-Schmuck, A Abravanel, F |
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| Keywords | Cirrhosis Hepatocellular carcinoma V3 domain Hepatitis C virus NS5A hepatitis C virus cirrhosis hepatocellular carcinoma |
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| Snippet | Highlights • Identification of a duplicated V3-NS5A domain in HCV1b strains infected French patients. • The prevalence of this strain in our multicenter cohort... •Identification of a duplicated V3-NS5A domain in HCV1b strains infected French patients.•The prevalence of this strain in our multicenter cohort was... The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. In a French multicenter study, we... Background The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. Objectives In a French... |
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| SubjectTerms | Adult Aged Allergy and Immunology Carcinoma, Hepatocellular - virology Cirrhosis Cross-Sectional Studies Female France Gene Duplication Hepacivirus - genetics Hepatitis C virus Hepatitis C, Chronic - virology Hepatocellular carcinoma Human health and pathology Humans Infectious Disease Life Sciences Liver Cirrhosis - virology Liver Neoplasms - virology Male Middle Aged Mutagenesis, Insertional NS5A Prevalence Protein Structure, Tertiary RNA, Viral - analysis Sequence Analysis, RNA V3 domain Viral Nonstructural Proteins - chemistry Viral Nonstructural Proteins - genetics |
| Title | Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients |
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