Simone Susser1, Julia Dietz1, Bernhard Schlevogt2, Eli Zuckerman3, Mira Barak4, Valeria Piazzolla5, Anita Howe6, Holger Hinrichsen7, Sandra Passmann1, Rasha Daniel4, Markus Cornberg8, Alessandra Mangia5, Stefan Zeuzem1, Christoph Sarrazin9. 1. Goethe-University Hospital, Medical Clinic 1, Frankfurt, Germany. 2. Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany. 3. Liver Unit, Carmel Medical Center and Rappaport Faculty of Medicine, The Technion, Haifa, Israel. 4. Haifa and Western Galilee Laboratory, Clalit Health Services, Nesher, Israel. 5. Liver Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. 6. British Columbia Center for Excellence for HIV/AIDS, Vancouver, Canada. 7. Gastroenterology, Gastroenterologische Schwerpunkt Praxis, Kiel, Germany. 8. Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany. 9. Goethe-University Hospital, Medical Clinic 1, Frankfurt, Germany; St. Josefs-Hospital, Medical Clinic 2, Wiesbaden, Germany. Electronic address: sarrazin@em.uni-frankfurt.de.
Abstract
BACKGROUND & AIMS: Little is known about the epidemiology and frequency of recombinant HCV genotype 2/1 strains, which may represent a challenge for direct antiviral therapy (DAA). This study aims to identify the epidemiology and phylogeny of HCV genotype 2/1 strains and encourages genotype screening, to select the DAA-regimen that achieves the optimal sustained virologic response. METHODS: Consecutive samples from HCV genotype 2 infected patients, according to commercial genotyping, from Germany, Italy and Israel were re-genotyped by Sanger-based sequencing. Virologic, epidemiological, and phylogenetic analyses including other published chimeras were performed. RESULTS: Sequence analysis of 442 supposed HCV genotype 2 isolates revealed 61 (genotype 2k/1b (n=59), 2a/1b (n=1) or 2b/1a (n=1)) chimeras. No chimeras were observed in Italy, but the frequency was 14% and 25% in Germany and Israel. Treatment of viral chimera with sofosbuvir/ribavirin led to virologic relapse in 25/27 patients (93%). Nearly all patients treated with genotype 1-based DAA-regimens initially (n=8/9), or after relapse (n=13/13), achieved a sustained virologic response. Most patients with 2k/1b chimeras (88%) were originally from eight different areas of the former Soviet Union. All known 2k/1b chimeras harbour the same recombination breakpoint and build one phylogenetic cluster, while all other chimeras have different phylogenies. CONCLUSIONS: The HCV genotype 2k/1b variant derives from one single recombination event most likely in the former Soviet Union, while other chimeras are unique and develop independently. A relatively high frequency has been observed along the migration flows, in Germany and Israel. In countries with little migration from the former Soviet Union the prevalence of 2k/1b chimeras is expected to be low. Treatment with sofosbuvir plus ribavirin is insufficient, but genotype 1-based regimens seem to be effective. Lay summary: The frequency of recombinant HCV is higher than expected. A novel recombinant variant (HCV genotype 2a/1b) was identified. Screening for recombinant viruses would contribute to increased response rates to direct antiviral therapy.
BACKGROUND & AIMS: Little is known about the epidemiology and frequency of recombinant HCV genotype 2/1 strains, which may represent a challenge for direct antiviral therapy (DAA). This study aims to identify the epidemiology and phylogeny of HCV genotype 2/1 strains and encourages genotype screening, to select the DAA-regimen that achieves the optimal sustained virologic response. METHODS: Consecutive samples from HCV genotype 2 infectedpatients, according to commercial genotyping, from Germany, Italy and Israel were re-genotyped by Sanger-based sequencing. Virologic, epidemiological, and phylogenetic analyses including other published chimeras were performed. RESULTS: Sequence analysis of 442 supposed HCV genotype 2 isolates revealed 61 (genotype 2k/1b (n=59), 2a/1b (n=1) or 2b/1a (n=1)) chimeras. No chimeras were observed in Italy, but the frequency was 14% and 25% in Germany and Israel. Treatment of viral chimera with sofosbuvir/ribavirin led to virologic relapse in 25/27 patients (93%). Nearly all patients treated with genotype 1-based DAA-regimens initially (n=8/9), or after relapse (n=13/13), achieved a sustained virologic response. Most patients with 2k/1b chimeras (88%) were originally from eight different areas of the former Soviet Union. All known 2k/1b chimeras harbour the same recombination breakpoint and build one phylogenetic cluster, while all other chimeras have different phylogenies. CONCLUSIONS: The HCV genotype 2k/1b variant derives from one single recombination event most likely in the former Soviet Union, while other chimeras are unique and develop independently. A relatively high frequency has been observed along the migration flows, in Germany and Israel. In countries with little migration from the former Soviet Union the prevalence of 2k/1b chimeras is expected to be low. Treatment with sofosbuvir plus ribavirin is insufficient, but genotype 1-based regimens seem to be effective. Lay summary: The frequency of recombinant HCV is higher than expected. A novel recombinant variant (HCV genotype 2a/1b) was identified. Screening for recombinant viruses would contribute to increased response rates to direct antiviral therapy.
Authors: Johannes Vermehren; Christoph Sarrazin; Kai-Henrik Peiffer; Lisa Kuhnhenn; Evelyn Stelzl; Julia Dietz; Simone Susser; Andrea Oliver Tal; Fabian Finkelmeier; Eli Zuckerman; Marcus Cornberg; Mira Barak; Valeria Piazzolla; Alessandra Mangia; Stefan Zeuzem; Harald H Kessler Journal: J Clin Microbiol Date: 2019-06-25 Impact factor: 5.948
Authors: Reilly Hostager; Manon Ragonnet-Cronin; Ben Murrell; Charlotte Hedskog; Anu Osinusi; Simone Susser; Christoph Sarrazin; Evguenia Svarovskaia; Joel O Wertheim Journal: Virus Evol Date: 2019-10-09
Authors: Carmen F Manso; David F Bibby; Kieren Lythgow; Hodan Mohamed; Richard Myers; David Williams; Renata Piorkowska; Yuen T Chan; Rory Bowden; M Azim Ansari; Camilla L C Ip; Eleanor Barnes; Daniel Bradshaw; Jean L Mbisa Journal: Front Microbiol Date: 2020-10-09 Impact factor: 5.640
Authors: Magda Bletsa; Bram Vrancken; Sophie Gryseels; Ine Boonen; Antonios Fikatas; Yiqiao Li; Anne Laudisoit; Sebastian Lequime; Josef Bryja; Rhodes Makundi; Yonas Meheretu; Benjamin Dudu Akaibe; Sylvestre Gambalemoke Mbalitini; Frederik Van de Perre; Natalie Van Houtte; Jana Těšíková; Elke Wollants; Marc Van Ranst; Oliver G Pybus; Jan Felix Drexler; Erik Verheyen; Herwig Leirs; Joelle Gouy de Bellocq; Philippe Lemey Journal: Virus Evol Date: 2021-04-12