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Khedhiri M, Ghedira K, Rajhi M, Hammemi W, Sadraoui A, Touzi H, Tebibi K, Chouikha A, Triki H. Overview of the epidemic history of Hepatitis C uncommon subtypes 2i and 4d in Tunisia and in the world. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2022; 105:105375. [PMID: 36241024 DOI: 10.1016/j.meegid.2022.105375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 09/06/2022] [Accepted: 10/07/2022] [Indexed: 11/05/2022]
Abstract
The impressive improvements in qua therapy efficacy alone are not sufficient to substantially reduce the Hepatitis C Virus burden because of the usually very long asymptomatic phase of the infection. In turn, this renders prevention of infection of great importance. The value of learning how the virus has spread in the past is that this can provide clues as to what routes the virus likely spreads through today, which can feedback into prevention policy. In Tunisia, HCV subtypes 2i and 4d are minor circulating subtypes. Here, we applied a Bayesian Markov Chain Monte Carlo method for visualization of spatial and temporal spread of HCV-2i and 4d in Tunisia and some other countries in the world. Our analysis included sequences retrieved from Genbank and isolated from several countries in the world; 21 HCV-NS5B subtype 2i genome sequences obtained during the period 2002-2020 and 206 HCV-NS5B-4d sequences detected between 2000 and 2019. Phylogenetic analysis revealed that two geographical clusters could be identified in HCV-2i tree with two clearly distinguished clusters in HCV-4d Tree. The estimated time for the most recent common ancestor suggested that current HCV-2i strains emerged in 1963 [1930, 1995] and current HCV-4d strains emerged in 1992 [1988, 1996] in Tunisia and other countries from the world investigated in the present study.
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Affiliation(s)
- Marwa Khedhiri
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Faculty of Sciences of Tunis, University of Tunis El Manar, Campus Universitaire, El Manar, Tunis 2092, Tunisia; Clinical Investigation Center (CIC), Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia.
| | - Kais Ghedira
- Laboratory of Bioinformatics, Biomathematics and Biostatistics - LR16IPT09, Pasteur Institute of Tunis, University Tunis El Manar, Tunis, Tunisia.
| | - Mouna Rajhi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia
| | - Walid Hammemi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Clinical Investigation Center (CIC), Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia
| | - Amel Sadraoui
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Clinical Investigation Center (CIC), Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia
| | - Henda Touzi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Clinical Investigation Center (CIC), Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia
| | - Khadija Tebibi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Faculty of Sciences of Tunis, University of Tunis El Manar, Campus Universitaire, El Manar, Tunis 2092, Tunisia
| | - Anissa Chouikha
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Clinical Investigation Center (CIC), Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia.
| | - Henda Triki
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia; Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", LR20IPT02, Pasteur Institute of Tunis, Tunisia; Clinical Investigation Center (CIC), Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis 1002, Tunisia.
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Rajhi M, Haddad-Boubaker S, Chouikha A, Bourquain D, Michel J, Hammami W, Sadraoui A, Touzi H, Ghedira K, Triki H. Identification of two novel hepatitis C virus subtype 2 from Tunisia (2v and 2w). PLoS One 2021; 16:e0248249. [PMID: 33705445 PMCID: PMC7951806 DOI: 10.1371/journal.pone.0248249] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 12/23/2020] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis C virus (HCV) has a high genetic diversity. Eight genotypes and 90 subtypes are currently described. Genotypes are clinically significant for therapeutic management and their determination is necessary for epidemiological studies. Methods Tunisian patients plasma samples (n = 6) with unassigned HCV-2 subtype using partial sequencing in the NS5B and Core/E1 regions were analyzed by realizing whole-genome sequencing analysis. Phylogenetic analyses were performed to assign subtypes. Results Phylogenetic analysis of the full genome sequences of Tunisian strains shows two subtypes within HCV-2. These later were genetically distinct from all previously established HCV-2 subtypes with nucleotide divergence greater than 15% (20% -31%). These two subtypes are proposed as new subtypes 2v and 2w. Conclusions The discovery of two new HCV-2 subtypes circulating in the Tunisian population confirms the great diversity of HCV-2 viruses and increases the total number of HCV-2 subtypes from 21 to 23.
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Affiliation(s)
- Mouna Rajhi
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
- * E-mail:
| | - Sondes Haddad-Boubaker
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
| | - Anissa Chouikha
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
| | - Daniel Bourquain
- Robert Koch Institute, Centre for Biological Threats and Special Pathogens–Highly Pathogenic Viruses, Berlin, Germany
| | - Janine Michel
- Robert Koch Institute, Centre for Biological Threats and Special Pathogens–Highly Pathogenic Viruses, Berlin, Germany
| | - Walid Hammami
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
| | - Amel Sadraoui
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
| | - Hinda Touzi
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
| | - Kais Ghedira
- University of Tunis El Manar, Tunis, Tunisia
- Laboratory of Bioinformatics, Biomathematics and Biostatistics (LR16IPT09), Pasteur Institute, Tunis, Tunisia
| | - Henda Triki
- Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles, for EMR, Pasteur Institute, Tunis, Tunisia
- University of Tunis El Manar, Tunis, Tunisia
- Research Laboratory of Virus, Vector and Host (LR20IPT10), Pasteur Institute, Tunis, Tunisia
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Ebranati E, Mancon A, Airoldi M, Renica S, Shkjezi R, Dragusha P, Della Ventura C, Ciccaglione AR, Ciccozzi M, Bino S, Tanzi E, Micheli V, Riva E, Galli M, Zehender G. Time and Mode of Epidemic HCV-2 Subtypes Spreading in Europe: Phylodynamics in Italy and Albania. Diagnostics (Basel) 2021; 11:diagnostics11020327. [PMID: 33671355 PMCID: PMC7922790 DOI: 10.3390/diagnostics11020327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/12/2021] [Accepted: 02/14/2021] [Indexed: 01/21/2023] Open
Abstract
Hepatitis C virus (HCV) genotype 2 causes about 10% of global infections and has the most variable circulation profile in Europe. The history of “endemic” HCV-2 subtypes has been satisfactorily reconstructed, instead there is little information about the recent spread of the “epidemic” subtypes, including HCV-2c. To investigate the origin and dispersion pathways of HCV-2c, 245 newly characterized Italian and Albanian HCV-2 NS5B sequences were aligned with 247 publicly available sequences and included in phylogeographic and phylodynamic analyses using the Bayesian framework. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania. The phylogeographic analysis suggested an African origin of HCV-2c before it reached Italy about in the 1940s. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in Italy between the 1940s and 1960s, and in Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonization but did not reach Albania until the period of dramatic migration to Italy in the 1990s. This study contributes to reconstructing the history of the spread of epidemic HCV-2 subtypes to Europe.
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Affiliation(s)
- Erika Ebranati
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; (E.E.); (M.A.); (S.R.); (C.D.V.); (M.G.)
- CRC-Coordinated Research Center “EpiSoMI”, University of Milan, 20122 Milan, Italy
| | - Alessandro Mancon
- Unit of Microbiology, Hospital Sacco of Milan, 20157 Milan, Italy; (A.M.); (V.M.)
| | - Martina Airoldi
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; (E.E.); (M.A.); (S.R.); (C.D.V.); (M.G.)
| | - Silvia Renica
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; (E.E.); (M.A.); (S.R.); (C.D.V.); (M.G.)
| | - Renata Shkjezi
- Faculty of Medicine and Surgery, Catholic University “Our Lady of the Good Counsel”, 1001 Tirana, Albania; (R.S.); (P.D.)
| | - Pranvera Dragusha
- Faculty of Medicine and Surgery, Catholic University “Our Lady of the Good Counsel”, 1001 Tirana, Albania; (R.S.); (P.D.)
| | - Carla Della Ventura
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; (E.E.); (M.A.); (S.R.); (C.D.V.); (M.G.)
| | - Anna Rita Ciccaglione
- Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy;
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, 00128 Roma, Italy;
| | - Silvia Bino
- National Institute of Health, 1001 Tirana, Albania;
| | - Elisabetta Tanzi
- Department of Biomedical Sciences for the Health, University of Milan, 20133 Milan, Italy;
| | - Valeria Micheli
- Unit of Microbiology, Hospital Sacco of Milan, 20157 Milan, Italy; (A.M.); (V.M.)
| | - Elisabetta Riva
- Laboratory of Virology, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Massimo Galli
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; (E.E.); (M.A.); (S.R.); (C.D.V.); (M.G.)
- CRC-Coordinated Research Center “EpiSoMI”, University of Milan, 20122 Milan, Italy
| | - Gianguglielmo Zehender
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy; (E.E.); (M.A.); (S.R.); (C.D.V.); (M.G.)
- CRC-Coordinated Research Center “EpiSoMI”, University of Milan, 20122 Milan, Italy
- Correspondence: ; Tel.: +39-02-503-19770
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Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore J. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol 2018; 10:807-821. [PMID: 30533182 PMCID: PMC6280160 DOI: 10.4254/wjh.v10.i11.807] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/10/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
The severity of hepatic pathology and the response to treatment depend on the hepatitis virus genotype in the infected host. The objective of this review was to determine the distribution of hepatitis virus genotypes in West African countries. A systematic review of the literature in PubMed, Google Scholar and Science Direct was performed to identify 52 relevant articles reporting hepatitis A, B, C, D, E and G viruses genotypes. Hepatitis B virus (HBV) genotype E with a prevalence of 90.6% (95%CI: 0.891-0.920) found in this review, is characterized by low genetic diversity. Hepatitis C virus (HCV) genotypes 1 and 2 represented 96.4% of HCV infections in West African countries, while hepatitis delta virus, hepatitis A virus, hepatitis G virus genotypes 1 and HEV genotype 3 were reported in some studies in Ghana and Nigeria. HBV genotype E is characterized by high prevalence, low genetic diversity and wide geographical distribution. Further studies on the clinical implications of HBV genotype E and HCV genotypes 1 and 2 are needed for the development of an effective treatment against this viral hepatitis in West African countries. Surveillance of the distribution of different genotypes is also needed to reduce recombination rates and prevent the emergence of more virulent viral strains.
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Affiliation(s)
- Maléki Assih
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Abdoul Karim Ouattara
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso.
| | - Birama Diarra
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Albert Theophane Yonli
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Tegwindé Rebeca Compaore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast 00233, Ghana
| | - Florencia Wendkuuni Djigma
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Simplice Karou
- Ecole Supérieure des Techniques Biologiques et Alimentaires (ESTBA-UL), Universite de Lome, Lome 00229, Togo
| | - Jacques Simpore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
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Schnell G, Tripathi R, Beyer J, Reisch T, Krishnan P, Dekhtyar T, Irvin M, Hall C, Yu Y, Mobashery N, Redman R, Pilot-Matias T, Collins C. Characterization of demographics and NS5A genetic diversity for hepatitis C virus genotype 4-infected patients with or without cirrhosis treated with ombitasvir/paritaprevir/ritonavir. J Viral Hepat 2018; 25:1078-1088. [PMID: 29624809 DOI: 10.1111/jvh.12906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 02/16/2018] [Indexed: 01/08/2023]
Abstract
Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse with 17 confirmed and 4 provisional subtypes. In this report, HCV GT4-infected patient samples from Phase 2/3 clinical studies were analysed to characterize global demographics and genetic diversity of GT4 infection among patients treated with ombitasvir (OBV, NS5A inhibitor) plus paritaprevir/r (NS3/4A inhibitor codosed with ritonavir). Among 17 subtypes isolated from GT4-infected patients in the PEARL-I and AGATE-I studies, subtype prevalence by country of enrolment and country of origin suggested that subtypes 4a and 4d were likely circulating in Europe, while heterogeneous GT4 subtypes and a portion of GT4a detected in European and North American countries were likely due to immigration of HCV-infected patients from Africa. The distributions of birth cohort and race were also significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. In addition, phylogenetic analyses of NS5A sequences revealed clustering within subtype 4a which segregated by the patient-reported country of origin and the presence of the L30R/S polymorphism. HCV NS5A sequences derived from GT4a-infected patients who originated from Europe and the United States clustered separately from sequences derived from patients who originated from Egypt, suggesting that genetically distinct strains of subtype 4a may be circulating globally. Finally, NS5A baseline polymorphisms were frequently detected at amino acid positions of interest for the inhibitor-class and OBV retained activity against 37 of 39 NS5A GT4 clinical isolates, with no impact on treatment outcome in the PEARL-I and AGATE-I studies.
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Affiliation(s)
- G Schnell
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - R Tripathi
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - J Beyer
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - T Reisch
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - P Krishnan
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - T Dekhtyar
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - M Irvin
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - C Hall
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - Y Yu
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - N Mobashery
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - R Redman
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - T Pilot-Matias
- Research & Development, AbbVie Inc., North Chicago, IL, USA
| | - C Collins
- Research & Development, AbbVie Inc., North Chicago, IL, USA
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Acero Fernández D, Ferri Iglesias MJ, Buxó Pujolràs M, López Nuñez C, Serra Matamala I, Queralt Molés X, Aldeguer Manté X. Changes in the epidemiology and distribution of the hepatitis C virus genotypes in North-Eastern Spain over the last 35 years. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 41:2-11. [PMID: 29150360 DOI: 10.1016/j.gastrohep.2017.09.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Revised: 09/02/2017] [Accepted: 09/15/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Genotypic distribution and epidemiology of HCV infection in Western Europe countries has changed over the last decades. AIM To establish the local genotypic profile and characterize the associated demographic variables. MATERIAL AND METHOD All the genotyping from 1988 to 2015 were considered. Associated demographic variables were included in logistic regression models. Genotyping was carried out with updated commercial kits. RESULTS Genotype 1b was the most prevalent (42.4%) followed by 1a (22.5%), 3 (18.6%), 4 (10.6%) and 2 (4.6%). The prevalence of 1a was higher in males, in patients younger than 45 and in intravenous drug users (IDU). 1b was more frequent in older than 45, with transfusion-associated and parenteral/nosocomial infections and in immigrants from Eastern Europe. Genotype 2 was highly prevalent in the postransfusional route (54.9%). Genotype 3 prevalence was high in males, in patients younger than 45, in IDU (69.3%) and in Asian and Eastern European immigrants. Genotype 4 was high in males, in patients younger than 45, and in IDU (63.5%). 1a, 3, 4 were the most prevalent genotypes in HIV-coinfected patients. There was a significant decline in genotype 1b and an increase in genotypes 3 and 4 over time. CONCLUSIONS There has been a decline of genotype 1b, associated with transfusion or parenteral/nosocomial infections, and increases in the prevalence of genotypes 1a, 3 and 4 associated with male gender and IDU, now the most prevalent infection route. Immigration contributed with genotype 2 infections from Africa and genotype 1b and 3 infections from Eastern Europe and Asia.
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Affiliation(s)
| | | | | | - Carmen López Nuñez
- Department of Digestive Diseases, Hospital de Girona, Doctor Josep Trueta, Girona, Spain
| | - Isabel Serra Matamala
- Department of Digestive Diseases, Hospital de Girona, Doctor Josep Trueta, Girona, Spain
| | | | - Xavier Aldeguer Manté
- Department of Digestive Diseases, Hospital de Girona, Doctor Josep Trueta, Girona, Spain; Institut de Investigacions Biomèdiques de Girona, IdIBGi, Salt, Spain
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7
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Rajhi M, Ghedira K, Chouikha A, Djebbi A, Cheikh I, Ben Yahia A, Sadraoui A, Hammami W, Azouz M, Ben Mami N, Triki H. Phylogenetic Analysis and Epidemic History of Hepatitis C Virus Genotype 2 in Tunisia, North Africa. PLoS One 2016; 11:e0153761. [PMID: 27100294 PMCID: PMC4839596 DOI: 10.1371/journal.pone.0153761] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 04/04/2016] [Indexed: 01/06/2023] Open
Abstract
HCV genotype 2 (HCV-2) has a worldwide distribution with prevalence rates that vary from country to country. High genetic diversity and long-term endemicity were suggested in West African countries. A global dispersal of HCV-2 would have occurred during the 20th century, especially in European countries. In Tunisia, genotype 2 was the second prevalent genotype after genotype 1 and most isolates belong to subtypes 2c and 2k. In this study, phylogenetic analyses based on the NS5B genomic sequences of 113 Tunisian HCV isolates from subtypes 2c and 2k were carried out. A Bayesian coalescent-based framework was used to estimate the origin and the spread of these subtypes circulating in Tunisia. Phylogenetic analyses of HCV-2c sequences suggest the absence of country-specific or time-specific variants. In contrast, the phylogenetic grouping of HCV-2k sequences shows the existence of two major genetic clusters that may represent two distinct circulating variants. Coalescent analysis indicated a most recent common ancestor (tMRCA) of Tunisian HCV-2c around 1886 (1869-1902) before the introduction of HCV-2k in 1901 (1867-1931). Our findings suggest that the introduction of HCV-2c in Tunisia is possibly a result of population movements between Tunisia and European population following the French colonization.
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Affiliation(s)
- Mouna Rajhi
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
- University of Carthage, Faculty of Sciences, Bizerte, Tunisia
- * E-mail:
| | - Kais Ghedira
- Pasteur Institute, Tunis, Tunisia; Laboratory of Bioinformatics, Mathematics and Statistics, Tunis, Tunisia
- University of Tunis El Manar, Tunis, 1036, Tunisia
| | - Anissa Chouikha
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
| | - Ahlem Djebbi
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
| | - Imed Cheikh
- Department of Gastroenterology, Regional Hospital of Bizerte, Bizerte, Tunisia
| | - Ahlem Ben Yahia
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
| | - Amel Sadraoui
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
| | - Walid Hammami
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
| | - Msaddek Azouz
- Department of Gastroenterology, Regional Hospital of Nabeul, Nabeul, Tunisia
| | - Nabil Ben Mami
- Department of Gastroenterology, La Rabta Hospital, Tunis, Tunisia
| | - Henda Triki
- Pasteur Institute, Tunis, Tunisia; Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Tunis, Tunisia
- University of Tunis El Manar, Tunis, 1036, Tunisia
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8
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Hepatitis C virus genotype 4 resistance and subtype demographic characterization of patients treated with ombitasvir plus paritaprevir/ritonavir. Antimicrob Agents Chemother 2015; 59:6807-15. [PMID: 26282418 PMCID: PMC4604390 DOI: 10.1128/aac.01229-15] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 08/09/2015] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography.
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Characterisation of hepatitis C virus genotype among blood donors at the regional blood transfusion centre of Ouagadougou, Burkina Faso. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2014; 12 Suppl 1:s54-7. [PMID: 24599906 DOI: 10.2450/2013.0089-12] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Accepted: 06/25/2012] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) is responsible for about 900 deaths every year in Burkina Faso. In this country, serological screening for hepatitis B and C viruses is only carried out systematically among blood donors. The aim of this study was to determine the prevalence and genotypes of HCV among blood donors using reverse transcription polymerase chain reaction (PCR) and real-time PCR, respectively. MATERIALS AND METHODS Serum samples were screened for antibodies to HCV using an enzyme-linked immunosorbent assay (ARCHITECT-i1000SR-ABBOTT). All the reactive samples for HCV antibodies were re-tested using a second enzyme-linked immunosorbent assay (Bio-Rad, Marnes la Coquette, France) for confirmation. RNA was detected in all the reactive samples for antibodies to HCV. HCV RNA positive samples were genotyped using the HCV Real-TM Genotype kit (Sacace Biotechnologies, Italy). RESULTS Among 2,200 blood donors, the prevalences of antibodies to HCV and viral RNA were 4.4% (95% confidence interval=3.5-5.3) and 1.5% (95% confidence interval=1.0-2.0), respectively. Among HCV RNA carriers, genotyping showed that HCV genotypes 2 and 3 were the most prevalent as they were detected in 18 (56.3%) and 5 (15.6%) individuals, respectively. HCV genotypes 1a and 4 were the least frequent among the blood donors. HCV mixed genotypes 2/3 and 2/4 were also detected among the blood donors. CONCLUSION The prevalence of HCV found in this study is lower than previously reported prevalences. Large-scale studies are needed to obtain a better picture of the molecular epidemiology of HCV in Burkina Faso.
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Ngui SL, Brant L, Markov PV, Tung JP, Pybus OG, Teo CG, Ramsay ME. Hepatitis C virus genotype 4 in England: diversity and demographic associations. J Med Virol 2014; 87:417-23. [PMID: 25185790 DOI: 10.1002/jmv.24069] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2014] [Indexed: 02/05/2023]
Abstract
HCV strains belonging to genotype 4 may be gaining endemicity across Continental Europe but the extent of their spread in the United Kingdom is unknown. Sera referred from patients attending hospitals in England between 2004 through 2008 were characterised. A total of 243 sera carried HCV genotype 4. The most common subtypes were 4a (33%) and 4d (35%). Compared to patients infected by 4d, those infected by 4a were 20 times more likely to be Middle Eastern than English, and those infected by non-4a/4d were older, tended to be female, and 50 or 12 times more likely to be Middle Eastern or South Asian, respectively, than English. Persons infected by 4d tended to be English rather than Middle Eastern or South Asian. One group of 4d strains clustered with strains reported from persons in Europe engaged in male homosexual activity. Surveillance of trends in the importation and subsequent spread of HCV genotype 4 and its subtypes is advocated.
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Back to the origin of HCV 2c subtype and spreading to the Calabria region (Southern Italy) over the last two centuries: a phylogenetic study. INFECTION GENETICS AND EVOLUTION 2014; 26:352-8. [PMID: 24973737 DOI: 10.1016/j.meegid.2014.06.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 05/23/2014] [Accepted: 06/09/2014] [Indexed: 12/12/2022]
Abstract
Circulation of HCV genotype 2 has been described in European Countries where numerous subtypes and unclassified HCV 2 lineages have been reported. In Italy, subtype 1b is the most prevalent, followed by genotype 2. In the present study, phylogeny of HCV 2c was investigated. The phylogeny of HCV 2c isolated from 54 Italian patients in the Calabria region (Southern Italy) was investigated by analyzing a fragment of the NS5B gene. Patients came from 5 metropolitan areas and a small village (Sersale). These areas were geographically dispersed throughout the entire region. A Bayesian coalescent-based framework was used to estimate origin and spreading of HCV 2c in this region. Phylogenetic analysis showed that 28 Italian sequences were intermixed with foreign HCV 2c reference sequences and grouped into 3 major clades: A, B, and C. Nineteen inter-clade sequences were associated uniquely with surgery as risk factor for HCV acquisition. By contrast, a sub-cluster within clade B was associated with blood transfusion. Moreover, sequences from Sersale village grouped in the Italian sub-cluster and were intermixed with 10 sequences from metropolitan areas. The three isolates with the longest branch came from Sersale and belonged to patients who had glass syringes as risk factor. HCV 2c isolates from the Calabria region shared a common ancestor whose origin was traced back to 1889. Our results suggest that, after its introduction - possibly as a result of population movements between Italy and African Countries during Italian colonialism - HCV 2c spread through multiple risk factors, not including intravenous drug use. So, transmission chains followed a pathway different from other European Countries. Although HCV incidence is decreasing, these ways are still ongoing, possibly justifying stability in the relative prevalence of HCV 2c.
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12
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Gonçalves Rossi LM, Rahal P. Challenges in molecular epidemiology of hepatitis C virus. J Clin Virol 2014; 60:174-6. [PMID: 24742600 DOI: 10.1016/j.jcv.2014.03.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Revised: 03/18/2014] [Accepted: 03/21/2014] [Indexed: 02/07/2023]
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13
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Evidence for two phylogenetic clusters within hepatitis C virus (HCV) genotype 2 inferred from analysis of complete coding sequences of 15 HCV strains. J Med Virol 2013; 85:1754-64. [DOI: 10.1002/jmv.23674] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2013] [Indexed: 02/05/2023]
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14
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Gu L, Tong W, Yuan M, Lu T, Li C, Lu L. An increased diversity of HCV isolates were characterized among 393 patients with liver disease in China representing six genotypes, 12 subtypes, and two novel genotype 6 variants. J Clin Virol 2013; 57:311-7. [PMID: 23706765 DOI: 10.1016/j.jcv.2013.04.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Revised: 03/26/2013] [Accepted: 04/22/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND We have recently determined HCV isolates among volunteer blood donors and IDUs in southern China and revealed the genotype distribution patterns not only different between the two studied cohorts but also from what we have sampled in 2002. A changed pattern could have also occurred among patients with liver disease. MATERIALS AND METHODS Both E1 and NS5B sequences of HCV were characterized among 393 patients with liver disease followed by phylogenetic analysis. RESULTS Six HCV genotypes, 12 subtypes (1b: 65.9%, 6a: 17.1%, 2a: 7.4%, 3a: 3.6%, 3b: in 3.3%, 6e: 0.76%, and 1a, 1c, 2b, 2f, 4d, and 5a each 0.25%), and two novel genotype 6 variants were classified, showing the greatest complexity of HCV hitherto found in China. Although the predominance of 1b followed by 6a is largely consistent with what we have sampled in 2002, the identification of single isolates of 1c, 2f, 4d, 5a, and two novel HCV-6 variants were first reported. Excluding 4d from a European visitor, all the others were from Chinese patients. Since the 6a proportion (17.1%, 67/393) was unexpectedly lower than what we have recently detected among blood donors (34.8%, 82/236) and IDUs (51.5%, 70/136), further statistical analyses were conducted. Comparison of the mean ages showed that among the 393 patients, those infected with 1b were significantly (6.7 years) older than those with 6a, while the 393 patients as a whole were significantly older than the 236 blood donors (8.4 years) and 136 IDUs (12.6 years) we have recently reported. Explanations are that younger individuals had higher proportions of 6a infections while patients with liver disease could have acquired their infections earlier than volunteer blood donors and IDUs. CONCLUSION Among 393 patients with liver disease, a great diversity in HCV was detected, which reflects a constantly changing pattern of HCV genotypes in China over time.
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Affiliation(s)
- Lin Gu
- Hepatology Laboratory, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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15
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Colonial history and contemporary transmission shape the genetic diversity of hepatitis C virus genotype 2 in Amsterdam. J Virol 2012; 86:7677-87. [PMID: 22573865 DOI: 10.1128/jvi.06910-11] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Evolutionary analysis of hepatitis C virus (HCV) genome sequences has provided insights into the epidemic history and transmission of this widespread human pathogen. Here we report an exceptionally diverse set of 178 HCV genotype 2 (HCV-2) isolates from 189 patients in Amsterdam, comprising 8 distinct HCV subtypes and 10 previously not recognized, unclassified lineages. By combining study subjects' demographic information with phylogeographic and molecular clock analyses, we demonstrate for the first time that the trans-Atlantic slave trade and colonial history were the driving forces behind the global dissemination of HCV-2. We detect multiple HCV-2 movements from present-day Ghana/Benin to the Caribbean during the peak years of the slave trade (1700 to 1850) and extensive transfer of HCV-2 among the Netherlands and its former colonies Indonesia and Surinam over the last 150 years. The latter coincides with the bidirectional migration of Javanese workers between Indonesia and Surinam and subsequent immigration to the Netherlands. In addition, our study sheds light on contemporary trends in HCV transmission within the Netherlands. We observe multiple lineages of the epidemic subtypes 2a, 2b, and 2c (together 67% of HCV-2 infections in Amsterdam), which cluster according to their suspected routes of transmission, specifically, injecting drug use (IDU) and contaminated blood/blood products. Understanding the epidemiological processes that generated the global pattern of HCV diversity seen today is critical for exposing associations between populations, risk factors, and specific HCV subtypes and might help HCV screening and prevention campaigns to minimize the future burden of HCV-related liver disease.
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16
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Li C, Cao H, Lu L, Murphy D. Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing five subtypes and six unclassified lineages with unique geographical distributions and genetic variation patterns. J Gen Virol 2012; 93:1173-1184. [PMID: 22357752 DOI: 10.1099/vir.0.038315-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In this study, we characterized full-length hepatitis C virus (HCV) genome sequences for 11 genotype 2 isolates. They were isolated from the sera of 11 patients residing in Canada, of whom four had an African origin. Full-length genomes, each with 18-25 overlapping fragments, were obtained by PCR amplification. Five isolates represent the first complete genomes of subtypes 2d, 2e, 2j, 2m and 2r, while the other six correspond to variants that do not group within any assigned subtypes. These sequences had lengths of 9508-9825 nt and each contained a single ORF encoding 3012-3106 aa. Predicted amino acids were carefully inspected and unique variation patterns were recognized, especially for a 2e isolate, QC64. Phylogenetic analysis of complete genome sequences provides evidence that there are a total of 16 subtypes, of which 11 have been described here. Co-analysis with 68 partial NS5B sequences also differentiated 18 assigned subtypes, 2a-2r, and eight additional lineages within genotype 2, which is consistent with the analysis of complete genome sequences. The data from this study will now allow 10 assigned subtypes and six additional lineages of HCV genotype 2 to have their full-length genomes defined. Further analysis with 2021 genotype 2 sequences available in the HCV database indicated that the geographical distribution of these subtypes is consistent with an African origin, with particular subtypes having spread to Asia and the Americas.
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Affiliation(s)
- Chunhua Li
- Cancer Research Center, University of Kansas Medical Center, Kansas City, KS, USA.,The Viral Oncology Center, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Hong Cao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Ling Lu
- Cancer Research Center, University of Kansas Medical Center, Kansas City, KS, USA.,The Viral Oncology Center, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Donald Murphy
- Institut national de santé publique du Québec, Laboratoire de santé publique du Québec, Sainte-Anne-de-Bellevue, QC, Canada
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Martró E, Valero A, Jordana-Lluch E, Saludes V, Planas R, González-Candelas F, Ausina V, Bracho MA. Hepatitis C virus sequences from different patients confirm the existence and transmissibility of subtype 2q, a rare subtype circulating in the metropolitan area of Barcelona, Spain. J Med Virol 2011; 83:820-6. [PMID: 21412791 DOI: 10.1002/jmv.22054] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The hepatitis C virus (HCV) has been classified into six genotypes and more than 70 subtypes with distinct geographical and epidemiological distributions. While 18 genotype 2 subtypes have been proposed, only 5 have had their complete sequence determined. The aim of this study was to characterize HCV isolates from three patients from the Barcelona metropolitan area of Spain for whom commercial genotyping methods provided discordant results. Full-length genome sequencing was carried out for 2 of the 3 patients; for the third patient only partial NS5B sequences could be obtained. The generated sequences were subjected to phylogenetic, recombination, and identity analyses. Sequences covering most of the HCV genome (9398 and 9566 nt in length) were obtained and showed a 90.3% identity to each other at the nucleotide level, while both sequences differed by 17.5-22.6% from the other fully sequenced genotype 2 subtypes. No evidence of recombination was found. The NS5B phylogenetic tree showed that sequences from the three patients cluster together with the only representative sequence of the provisionally designed 2q subtype, which also corresponds to a patient from Barcelona. Phylogenetic analysis of the full coding sequence showed that subtype 2q was more closely related to subtype 2k. The results obtained in this study suggest that subtype 2q now meets the requirements for confirmed designation status according to consensus criteria for HCV classification and nomenclature, and its epidemiological value is ensured as it has spread among several patients in the Barcelona metropolitan area.
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Affiliation(s)
- Elisa Martró
- Microbiology Service, Health Sciences Research Institute of Germans Trias i Pujol Foundation, Germans Trias i Pujol Hospital, Autonoma University of Barcelona, Badalona, Spain.
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18
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Ré VE, Culasso ACA, Mengarelli S, Farías AA, Fay F, Pisano MB, Elbarcha O, Contigiani MS, Campos RH. Phylodynamics of hepatitis C virus subtype 2c in the province of Córdoba, Argentina. PLoS One 2011; 6:e19471. [PMID: 21611129 PMCID: PMC3097208 DOI: 10.1371/journal.pone.0019471] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 03/30/2011] [Indexed: 01/31/2023] Open
Abstract
The Hepatitis C Virus Genotype 2 subtype 2c (HCV-2c) is detected as a low prevalence subtype in many countries, except in Southern Europe and Western Africa. The current epidemiology of HCV in Argentina, a low-prevalence country, shows the expected low prevalence for this subtype. However, this subtype is the most prevalent in the central province of Córdoba. Cruz del Eje (CdE), a small rural city of this province, shows a prevalence for HCV infections of 5%, being 90% of the samples classified as HCV-2c. In other locations of Córdoba Province (OLC) with lower prevalence for HCV, HCV-2c was recorded in about 50% of the samples. The phylogenetic analysis of samples from Córdoba Province consistently conformed a monophyletic group with HCV-2c sequences from all the countries where HCV-2c has been sequenced. The phylogeographic analysis showed an overall association between geographical traits and phylogeny, being these associations significant (α = 0.05) for Italy, France, Argentina (places other than Córdoba), Martinique, CdE and OLC. The coalescence analysis for samples from CdE, OLC and France yielded a Time for the Most Common Recent Ancestor of about 140 years, whereas its demographic reconstruction showed a “lag” phase in the viral population until 1880 and then an exponential growth until 1940. These results were also obtained when each geographical area was analyzed separately, suggesting that HCV-2c came into Córdoba province during the migration process, mainly from Europe, which is compatible with the history of Argentina of the early 20th century. This also suggests that the spread of HCV-2c occurred in Europe and South America almost simultaneously, possibly as a result of the advances in medicine technology of the first half of the 20th century.
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Affiliation(s)
- Viviana E. Ré
- Facultad de Ciencias Médicas, Instituto de Virología, Universidad de Córdoba, Córdoba, Argentina
- Cátedra de Virología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina
| | - Andrés C. A. Culasso
- Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Silvia Mengarelli
- Servicio de Gastroenterología, Hospital San Roque, Córdoba, Argentina
| | - Adrián A. Farías
- Facultad de Ciencias Médicas, Instituto de Virología, Universidad de Córdoba, Córdoba, Argentina
| | - Fabián Fay
- Laboratorio CIBIC, Centro de Diagnóstico Moleculares, Rosario, Argentina
| | - María B. Pisano
- Facultad de Ciencias Médicas, Instituto de Virología, Universidad de Córdoba, Córdoba, Argentina
| | - Osvaldo Elbarcha
- Cátedra de Virología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina
| | - Marta S. Contigiani
- Facultad de Ciencias Médicas, Instituto de Virología, Universidad de Córdoba, Córdoba, Argentina
| | - Rodolfo H. Campos
- Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
- * E-mail:
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Eriksen MB, Jørgensen LB, Krarup H, Laursen AL, Christensen PB, Møller A, Schlichting P, Kuiken C, Bukh J, Weis N. Molecular and epidemiological profiles of hepatitis C virus genotype 4 in Denmark. J Med Virol 2011; 82:1869-77. [PMID: 20872713 DOI: 10.1002/jmv.21896] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The prevalence of hepatitis C virus (HCV) genotype 4 has increased throughout Europe. This is an epidemiological study of patients infected chronically with HCV genotype 4 in Denmark. The HCV strains analyzed originated from patient samples collected between 1999 and 2007 as part of the national Danish hepatitis B and C network, DANHEP. Sequence analyses were based on the envelope 1 region of HCV. Results from a total of 72 patients indicated a high degree of genetic heterogeneity. Fifty-six patients (78%) were infected with one of the three dominating subtypes: 4d, 4a, or 4r. The remaining 16 patients (22%) were infected with subtypes 4h, 4k, 4l, 4n, 4o, or 4Unclassified. Three epidemiological profiles were identified: (1) patients infected with HCV by intravenous drug use were infected solely with subtype 4d. They were all of European origin, and 15 of the 16 patients were ethnic Danes. No single transmission event could be confirmed, but the pairwise nucleotide identity within the patients of Danish origin was relatively high (∼95%), suggesting a recent introduction into Denmark. (2) The 21 patients infected with subtype 4a all came from Northern Africa, Egypt, Pakistan, or the Middle East. (3) Patients from Southern Africa dominated among patients infected with subtype 4r (10 of 12 patients). This study demonstrates that HCV genotype 4d has been introduced in and spread among Danish intravenous drug users. The remaining subtypes show restricted distribution, infecting almost exclusively patients from geographical areas with a relatively high prevalence of HCV genotype 4 infections.
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20
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Sulbarán MZ, Di Lello FA, Sulbarán Y, Cosson C, Loureiro CL, Rangel HR, Cantaloube JF, Campos RH, Moratorio G, Cristina J, Pujol FH. Genetic history of hepatitis C virus in Venezuela: high diversity and long time of evolution of HCV genotype 2. PLoS One 2010; 5:e14315. [PMID: 21179440 PMCID: PMC3001475 DOI: 10.1371/journal.pone.0014315] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2010] [Accepted: 11/19/2010] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The subtype diversity of the hepatitis C virus (HCV) genotypes is unknown in Venezuela. METHODOLOGY/PRINCIPAL FINDINGS Partial sequencing of the NS5B region was performed in 310 isolates circulating in patients from 1995 to 2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1) was the most common genotype (63%), composed as expected of mainly G1a and G1b. G2 was the second most common genotype (33%), being G2a almost absent and G2j the most frequent subtype. Sequence analysis of the core region confirmed the subtype assignment performed within the NS5b region in 63 isolates. The complete genome sequence of G2j was obtained. G2j has been described in France, Canada and Burkina Fasso, but it was not found in Martinique, where several subtypes of G2 circulate in the general population. Bayesian coalescence analysis indicated a most recent common ancestor (MRCA) of G2j around 1785, before the introduction of G1b (1869) and G1a (1922). While HCV G1a and G1b experienced a growth reduction since 1990, coincident with the time when blood testing was implemented in Venezuela, HCV G2j did not seem to reach growth equilibrium during this period. CONCLUSIONS/SIGNIFICANCE Assuming the introduction of G2j from Africa during the slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the introduction of African ethnic groups different from the ones introduced to Martinique or 2- the occurrence of a founder effect. This study represents an in-depth analysis of the subtype diversity of HCV in Venezuela, which is still unexplored in the Americas and deserves further studies.
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Affiliation(s)
| | - Federico A. Di Lello
- Cátedra de Virología de la Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Yoneira Sulbarán
- Laboratorio de Virología Molecular, CMBC, IVIC, Caracas, Venezuela
| | - Clarisa Cosson
- Laboratorio de Virología Molecular, CMBC, IVIC, Caracas, Venezuela
| | | | - Héctor R. Rangel
- Laboratorio de Virología Molecular, CMBC, IVIC, Caracas, Venezuela
| | - Jean F. Cantaloube
- Unité Emergence et Co-évolution virale, Etablissement Français du Sang Alpes-Méditerranée, Marseille, France
| | - Rodolfo H. Campos
- Cátedra de Virología de la Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Gonzalo Moratorio
- Departamento de Técnicas Nucleares Aplicadas, Facultad de Ciencias, Centro de Investigaciones Nucleares, Universidad de la República, Montevideo, Uruguay
- Unidad de Biofísica de Proteínas, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Juan Cristina
- Departamento de Técnicas Nucleares Aplicadas, Facultad de Ciencias, Centro de Investigaciones Nucleares, Universidad de la República, Montevideo, Uruguay
| | - Flor H. Pujol
- Laboratorio de Virología Molecular, CMBC, IVIC, Caracas, Venezuela
- * E-mail:
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Cantaloube JF, Gallian P, Bokilo A, Jordier F, Biagini P, Attoui H, Chiaroni J, de Micco P. Analysis of hepatitis C virus strains circulating in Republic of the Congo. J Med Virol 2010; 82:562-7. [PMID: 20166180 DOI: 10.1002/jmv.21724] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The aim of this study was to assess the seroprevalence, viremia, genotype distribution, and demographic history of hepatitis C virus (HCV) in the Republic of the Congo. Testing was carried out on sera samples collected in 2005 from 807 Bantus belonging to the Kongo, Teke, and Ngala subgroups and 80 Pygmies. Positive HCV serology was found in 50 (5.6%) individuals including 31 (60%) who were viremic. Seroprevalence increased with age with a cutoff at 50 years: 2.8% <50 versus 12% >50. Twenty-one strains belonged to four described subtypes, that is, 4c in eight cases, 4h in two, 4k in three, and 4r in eight. Ten strains could not be assigned to any known subtype and may represent six new variants, that is, subtype 4 in five cases and subtype 2 in one. Evolutionary analysis of subtype 4c and 4r sequences indicated a period of enhanced transmission in the mid-twentieth century probably due to iatrogenic causes. This study underlines the high genetic diversity of strains in the Republic of the Congo with nine subtypes 4 and one subtype 2.
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Affiliation(s)
- Jean-François Cantaloube
- Viral Emergence and Co-evolution Department, UMR 6578, CNRS, University of the Mediterranean, EFS Alpes-Méditerranée, Marseille, France.
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Njouom R, Frost E, Deslandes S, Mamadou-Yaya F, Labbé AC, Pouillot R, Mbélesso P, Mbadingai S, Rousset D, Pépin J. Predominance of hepatitis C virus genotype 4 infection and rapid transmission between 1935 and 1965 in the Central African Republic. J Gen Virol 2009; 90:2452-2456. [PMID: 19535500 DOI: 10.1099/vir.0.011981-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The molecular epidemiology of hepatitis C virus (HCV) in the Central African Republic (CAR) is poorly documented. Thus, we conducted phylogenetic analyses of NS5B gene sequences from 58 HCV-infected inhabitants of a remote area of south-west CAR, which indicated that 48 (82.8%) were infected with genotype 4 (HCV-4), five (8.6%) with genotype 2 and five (8.6%) with genotype 1. HCV-4 strains were highly heterogeneous, containing previously described subtypes 4k (48%), 4c (27%), 4r (4%), 4f (4%) and unclassified subtypes (17%). To estimate the epidemic history of these HCV-4 strains, an evolutionary analysis using the coalescent approach was used. The estimated date of the most recent common ancestor of the CAR HCV-4 strains was 1539 (95% confidence intervals, 1317-1697). They exhibited a rapid, exponential spread from 1935 to 1965, simultaneously with what was recently reported in neighbouring Cameroon and Gabon. The hypothesis of a massive iatrogenic transmission during interventions for the control of endemic tropical diseases is discussed.
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Affiliation(s)
- Richard Njouom
- Laboratoire de Virologie, Centre Pasteur du Cameroun, Yaoundé, Cameroon
| | - Eric Frost
- Département de Microbiologie et Infectiologie, Université de Sherbrooke, Canada
| | - Sylvie Deslandes
- Département de Microbiologie et Infectiologie, Université de Sherbrooke, Canada
| | | | - Annie-Claude Labbé
- Department of Microbiology, Hôpital Maisonneuve-Rosemont, Montréal, Canada
| | - Régis Pouillot
- Laboratoire d'Épidémiologie, Centre Pasteur du Cameroun, Yaoundé, Cameroon
| | | | | | - Dominique Rousset
- Laboratoire de Virologie, Centre Pasteur du Cameroun, Yaoundé, Cameroon
| | - Jacques Pépin
- Département de Microbiologie et Infectiologie, Université de Sherbrooke, Canada
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Chevaliez S, Bouvier-Alias M, Castéra L, Pawlotsky JM. The Cobas AmpliPrep-Cobas TaqMan real-time polymerase chain reaction assay fails to detect hepatitis C virus RNA in highly viremic genotype 4 clinical samples. Hepatology 2009; 49:1397-8. [PMID: 19330876 DOI: 10.1002/hep.22767] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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