scholarly journals Risk Factors for Infection with Different Hepatitis C Virus Genotypes in Southern Brazil

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Marisa Lúcia Romani Paraboni ◽  
Marina Dallagasperina Sbeghen ◽  
Fernando Herz Wolff ◽  
Leila Beltrami Moreira
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Multinomial Logistic Regression ◽  
Patient Treatment ◽  
Treatment Center ◽  
Southern Brazil ◽  
Genotype 1 ◽  
Convenience Sample ◽  
Genotype 2

Objectives. To investigate the proportion of different genotypes in countryside microregions in southern Brazil, and their association with risk factors.Methods. Cross-sectional study including a convenience sample of patients who tested positive for HCV-RNA and were referred to a regional health center for genotyping, from December 2003 to January 2008. Data were obtained through the National Disease Surveillance Data System, from laboratory registers and from patient charts. Identification of genotypes was carried out using the Restriction Fragment Length Polymorphism “in house” technique. Independent associations with genotypes were evaluated in multinomial logistic regression and prevalence rates of genotypes were estimated with modified Poisson regression.Results. The sample consisted of 441 individuals, years old, 56.5% men. Genotype 1 was observed in 41.5% (95% CI 37.9–48.1) of patients, genotype 2 in 19.3% (95% CI 15.0–23.6), and genotype 3 in 39.2% (95% CI 35.6–43.0). HCV genotype was significantly associated with gender and age. Dental procedures were associated with higher proportion of genotype 2 independently of age, education, and patient treatment center.Conclusions. The hepatitis C virus genotype 1 was the most frequent. Genotype 2 was associated with female gender, age, and dental procedure exposition.

scholarly journals Preclinical Characterization of BMS-791325, an Allosteric Inhibitor of Hepatitis C Virus NS5B Polymerase

2014 ◽  
Vol 58 (6) ◽  
pp. 3485-3495 ◽  
Author(s):  
Julie A. Lemm ◽  
Mengping Liu ◽  
Robert G. Gentles ◽  
Min Ding ◽  
Stacey Voss ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nucleoside Analogs ◽  
Synergistic Activity ◽  
Genotype 1 ◽  
Allosteric Inhibitor ◽  
Genotype 2 ◽  
Hcv Genotype 1 ◽  
Ns3 Protease

ABSTRACTBMS-791325 is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. Potency against genotype 6a showed more variability (9 to 125 nM), and activity was weaker against genotype 2 (EC50, 87 to 925 nM). Specificity was demonstrated by the absence of activity (EC50s of >4 μM) against a panel of mammalian viruses, and cytotoxic concentrations (50%) were >3,000-fold above the HCV EC50. Resistance substitutions selected by BMS-791325 in genotype 1 replicons mostly mapped to a single site, NS5B amino acid 495 (P495A/S/L/T). Additive or synergistic activity was observed in combination studies using BMS-791325 with alfa interferon plus ribavirin, inhibitors of NS3 protease or NS5A, and other classes of NS5B inhibitor (palm site 2-binding or nucleoside analogs). Plasma and liver exposuresin vivoin several animal species indicated that BMS-791325 has a hepatotropic disposition (liver-to-plasma ratios ranging from 1.6- to 60-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥10-fold above the inhibitor EC50s observed with HCV genotype 1 replicons. These findings support the evaluation of BMS-791325 in combination regimens for the treatment of HCV. Phase 3 studies are ongoing.

scholarly journals Epidemic history of hepatitis C virus infection in two remote communities in Nigeria, West Africa

2012 ◽  
Vol 93 (7) ◽  
pp. 1410-1421 ◽  
Author(s):  
Joseph C. Forbi ◽  
Michael A. Purdy ◽  
David S. Campo ◽  
Gilberto Vaughan ◽  
Zoya E. Dimitrova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
20Th Century ◽  
Hypervariable Region ◽  
Hcv Infection ◽  
Genotype 1 ◽  
Remote Communities ◽  
African Countries ◽  
Genotype 2 ◽  
History Of

We investigated the molecular epidemiology and population dynamics of HCV infection among indigenes of two semi-isolated communities in North-Central Nigeria. Despite remoteness and isolation, ~15 % of the population had serological or molecular markers of hepatitis C virus (HCV) infection. Phylogenetic analysis of the NS5b sequences obtained from 60 HCV-infected residents showed that HCV variants belonged to genotype 1 (n = 51; 85 %) and genotype 2 (n = 9; 15 %). All sequences were unique and intermixed in the phylogenetic tree with HCV sequences from people infected from other West African countries. The high-throughput 454 pyrosequencing of the HCV hypervariable region 1 and an empirical threshold error correction algorithm were used to evaluate intra-host heterogeneity of HCV strains of genotype 1 (n = 43) and genotype 2 (n = 6) from residents of the communities. Analysis revealed a rare detectable intermixing of HCV intra-host variants among residents. Identification of genetically close HCV variants among all known groups of relatives suggests a common intra-familial HCV transmission in the communities. Applying Bayesian coalescent analysis to the NS5b sequences, the most recent common ancestors for genotype 1 and 2 variants were estimated to have existed 675 and 286 years ago, respectively. Bayesian skyline plots suggest that HCV lineages of both genotypes identified in the Nigerian communities experienced epidemic growth for 200–300 years until the mid-20th century. The data suggest a massive introduction of numerous HCV variants to the communities during the 20th century in the background of a dynamic evolutionary history of the hepatitis C epidemic in Nigeria over the past three centuries.

scholarly journals SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells

2009 ◽  
Vol 47 (10) ◽  
Author(s):  
Marcello Persico ◽  
Roberta Russo ◽  
Eliana Persico ◽  
Monica Svelto ◽  
Daniela Spano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepg2 Cells ◽  
Genotype 1 ◽  
Genotype 2

scholarly journals Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants:In VitroSelection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle

2016 ◽  
Vol 60 (6) ◽  
pp. 3563-3578 ◽  
Author(s):  
Stéphanie B. N. Serre ◽  
Sanne B. Jensen ◽  
Lubna Ghanem ◽  
Daryl G. Humes ◽  
Santseharay Ramirez ◽  
...  
Keyword(s):  
Life Cycle ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hot Spots ◽  
Viral Life Cycle ◽  
Viral Fitness ◽  
Cross Resistance ◽  
Genotype 1 ◽  
Genotype 2 ◽  
Ns3 Protease

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research.

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