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High prevalence of hepatitis C virus genotype 1b infection in a small town of Argentina. Phylogenetic and Bayesian coalescent analysis.

ABSTRACT: Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina).A total of 89 out of 1814 blood samples collected from people living in Wheelwright, were positive for HCV infection. The highest prevalence (4.9%) was observed in people older than 50 years, with the highest level for the group aged between 70-79 years (22%). The RFLP analyses showed that 91% of the positive samples belonged to the HCV-1b genotype. The E1/E2 and NS5B genes were sequenced, and their phylogenetic analysis showed that the HCV-1b sequences from Wheelwright were monophyletic. Bayesian coalescent-based methods were used to estimate substitution rates and time of the most recent common ancestor (tMRCA). The mean estimated substitution rates and the tMRCA for E1/E2 with and without HVR1 and NS5B were 7.41E-03 s/s/y and 61 years, 5.05E-03 s/s/y and 58 years and 3.24E-03 s/s/y and 53 years, respectively. In summary, the tMRCA values, the demographic model with constant population size, and the fact that the highest prevalence of infection was observed in elder people support the hypothesis that the HCV-1b introduction in Wheelwright initially occurred at least five decades ago and that the early epidemic was characterized by a fast rate of virus transmission. The epidemic seems to have been controlled later on down to the standard transmission rates observed elsewhere.

SUBMITTER: Golemba MD

PROVIDER: S-EPMC2807465 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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High prevalence of hepatitis C virus genotype 1b infection in a small town of Argentina. Phylogenetic and Bayesian coalescent analysis.

Golemba Marcelo D MD Di Lello Federico A FA Bessone Fernando F Fay Fabian F Benetti Silvina S Jones Leandro R LR Campos Rodolfo H RH

PloS one 20100118 1

Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina).A total of 89 out of 1814 blood samples collected from people living in Wheelw ...[more]

PMID: 20090919

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Project description:UnlabelledBecause of recent advances in deep sequencing technology, detailed analysis of hepatitis C virus (HCV) quasispecies and their dynamic changes in response to direct antiviral agents (DAAs) became possible, although the role of quasispecies is not fully understood. In this study, to clarify the evolution of viral quasispecies and the origin of drug-resistant mutations induced by interferon (IFN)-based protease inhibitor therapy, the nonstructural-3 (NS3) region of genotype 1b HCV in 34 chronic hepatitis patients treated with telaprevir (TVR)/pegylated interferon (PEG-IFN)/ribavirin (RBV) was subjected to a deep sequencing study coupled with phylogenetic analysis. Twenty-six patients (76.5%) achieved a sustained viral response (SVR), while 8 patients did not (non-SVR; 23.5%). When the complexity of the quasispecies was expressed as the mutation frequency or Shannon entropy value, a significant decrease in the IFNL3 (rs8099917) TT group and a marginal decrease in the SVR group were found soon (12 h) after the introduction of treatment, whereas there was no decrease in the non-SVR group and no significant decrease in mutation frequency in the IFNL3 TG/GG group. In the analysis of viral quasispecies composition in non-SVR patients, major populations greatly changed, accompanied by the appearance of resistance, and the compositions were unlikely to return to the pretreatment composition even after the end of therapy. Clinically TVR-resistant variants were observed in 5 non-SVR patients (5/8, 62.5%), all of which were suspected to have acquired resistance by mutations through phylogenetic analysis. In conclusion, results of the study have important implications for treatment response and outcome in interferon-based protease inhibitor therapy.ImportanceIn the host, hepatitis C virus (HCV) consists of a variety of populations (quasispecies), and it is supposed that dynamic changes in quasispecies are closely related to pathogenesis, although this is poorly understood. In this study, recently developed deep sequencing technology was introduced, and changes in quasispecies associated with telaprevir (TVR)/pegylated interferon (PEG-IFN)/ribavirin (RBV) triple therapy and their clinical significance were investigated extensively by phylogenetic tree analysis. Through this study, the associations among treatment response, changes in viral quasispecies complexity in the early stage of treatment, changes in the quasispecies composition, and origin of TVR-resistant variant HCV were elucidated.

Project description:AimIn order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections).ResultsOverall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896.DiscussionHBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.

Dataset Information

High prevalence of hepatitis C virus genotype 1b infection in a small town of Argentina. Phylogenetic and Bayesian coalescent analysis.

Publications

High prevalence of hepatitis C virus genotype 1b infection in a small town of Argentina. Phylogenetic and Bayesian coalescent analysis.

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