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Despite the advent of direct-acting antivirals (DAAs), challenges in diagnosis and treatment remain, compounded by the lack of an effective vaccine. The HCV genome, characterized by high genetic variability, consists of eight distinct genotypes and over ninety subtypes, underscoring the complex dynamics of the virus within infected individuals. This study delves into the intriguing realm of HCV genetic diversity, specifically exploring the phenomenon of mixed infections and the subsequent detection of recombinant forms within the conserved internal ribosome entry site (IRES) region. Previous studies have identified recombination as a rare event in HCV. However, our findings challenge this notion by providing the first evidence of 1a\/3a (and vice versa) inter-genotypic recombination within the conserved IRES region. Utilizing advanced sequencing methods, such as deep sequencing and molecular cloning, our study reveals mixed infections involving genotypes 1a and 3a. This comprehensive approach not only confirmed the presence of mixed infections, but also identified the existence of recombinant forms not previously seen in the IRES region. The recombinant sequences, although present as low-frequency variants, open new avenues for understanding HCV evolution and adaptation.<\/jats:p>","DOI":"10.3390\/v16040560","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T08:42:34Z","timestamp":1712133754000},"page":"560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mixed Infections Unravel Novel HCV Inter-Genotypic Recombinant Forms within the Conserved IRES Region"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-6051","authenticated-orcid":false,"given":"Natalia","family":"Echeverr\u00eda","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"},{"name":"Laboratorio de Evoluci\u00f3n Experimental de Virus, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"G\u00e1mbaro","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-6425","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Beaucourt","sequence":"additional","affiliation":[{"name":"Viral Populations and Pathogenesis Laboratory, Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-6117","authenticated-orcid":false,"given":"Mart\u00edn","family":"So\u00f1ora","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"},{"name":"Laboratorio de Simulaciones Biomoleculares, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelia","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Cl\u00ednica de Gastroenterolog\u00eda, Hospital de Cl\u00ednicas, Facultad de Medicina, Universidad de la Rep\u00fablica, Montevideo 11600, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Cristina","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Moratorio","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"},{"name":"Laboratorio de Evoluci\u00f3n Experimental de Virus, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6155-7206","authenticated-orcid":false,"given":"Pilar","family":"Moreno","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"},{"name":"Laboratorio de Evoluci\u00f3n Experimental de Virus, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, February 14). Hepatitis C, Fact Sheet. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-c."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.jhep.2016.07.035","article-title":"The History of Hepatitis C Virus (HCV): Basic Research Reveals Unique Features in Phylogeny, Evolution and the Viral Life Cycle with New Perspectives for Epidemic Control","volume":"65","author":"Bukh","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1128\/jvi.66.3.1476-1483.1992","article-title":"Internal Ribosome Entry Site within Hepatitis C Virus RNA","volume":"66","author":"Iizuka","year":"1992","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/hep.26744","article-title":"Expanded Classification of Hepatitis C Virus into 7 Genotypes and 67 Subtypes: Updated Criteria and Genotype Assignment Web Resource","volume":"59","author":"Smith","year":"2014","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/infdis\/jiy401","article-title":"Identification of a Novel Hepatitis C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 Genotypes","volume":"218","author":"Borgia","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_6","unstructured":"Simmonds, P. (1994). Current Studies in Hematology and Blood Transfusion, Karger."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1099\/0022-1317-76-7-1749","article-title":"Variation of the Hepatitis C Virus 5\u2032 Non-Coding Region: Implications for Secondary Structure, Virus Detection and Typing. The International HCV Collaborative Study Group","volume":"76 Pt 7","author":"Smith","year":"1995","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s00239-001-0018-9","article-title":"Hepatitis C Virus Evolutionary Patterns Studied Through Analysis of Full-Genome Sequences","volume":"54","author":"Salemi","year":"2002","journal-title":"J. Mol. Evol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1261\/rna.5950603","article-title":"Structural Organization of a Viral IRES Depends on the Integrity of the GNRA Motif","volume":"9","year":"2003","journal-title":"RNA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1093\/nar\/gkn1022","article-title":"Analysis of Natural Variants of the Hepatitis C Virus Internal Ribosome Entry Site Reveals That Primary Sequence Plays a Key Role in Cap-Independent Translation","volume":"37","author":"Vollrath","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1093\/nar\/gkv1325","article-title":"LOOP IIId of the HCV IRES Is Essential for the Structural Rearrangement of the 40S-HCV IRES Complex","volume":"44","author":"Angulo","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1128\/JVI.01047-12","article-title":"Rapid Intracellular Competition between Hepatitis C Viral Genomes as a Result of Mitosis","volume":"87","author":"Webster","year":"2013","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1128\/JVI.01748-06","article-title":"Superinfection Exclusion in Cells Infected with Hepatitis C Virus","volume":"81","author":"Tscherne","year":"2007","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.3390\/v3102006","article-title":"Recombination in Hepatitis C Virus","volume":"3","author":"Bracho","year":"2011","journal-title":"Viruses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1128\/JVI.76.8.4034-4043.2002","article-title":"A Natural Intergenotypic Recombinant of Hepatitis C Virus Identified in St. Petersburg","volume":"76","author":"Kalinina","year":"2002","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/1743-422X-3-95","article-title":"Serendipitous Identification of Natural Intergenotypic Recombinants of Hepatitis C in Ireland","volume":"3","author":"Moreau","year":"2006","journal-title":"Virol. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.jiac.2018.04.001","article-title":"Case Report: Identification of Recombinant HCV Genotype 1b\u20132b by Viral Sequencing in Two Patients with Treatment Failure, Who Responded to Re-Treatment with Sofosbuvir and Daclatasvir","volume":"24","year":"2018","journal-title":"J. Infect. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shi, W., Freitas, I.T., Zhu, C., Zheng, W., Hall, W.W., and Higgins, D.G. (2012). Recombination in Hepatitis C Virus: Identification of Four Novel Naturally Occurring Inter-Subtype Recombinants. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041997"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1128\/JCM.00483-15","article-title":"Characterization of Hepatitis C Virus Recombination in Cameroon by Use of Nonspecific Next-Generation Sequencing","volume":"53","author":"Iles","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4137\/EBO.S1038","article-title":"Evidence for a Complex Mosaic Genome Pattern in a Full-Length Hepatitis C Virus Sequence","volume":"4","author":"Ross","year":"2008","journal-title":"Evol. Bioinform. Online"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/jmv.21658","article-title":"Molecular Epidemiology of HCV Genotypes among Injection Drug Users in Taiwan: Full-Length Sequences of Two New Subtype 6w Strains and a Recombinant Form-2b6w","volume":"82","author":"Lee","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1186\/1743-422X-8-458","article-title":"Naturally Occurring Genotype 2b\/1a Hepatitis C Virus in the United States","volume":"8","author":"Bhattacharya","year":"2011","journal-title":"Virol. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1007\/s00705-011-1038-4","article-title":"Identification and Characterization of a Natural Inter-Genotypic (2b\/1b) Recombinant Hepatitis C Virus in Japan","volume":"156","author":"Yokoyama","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/jmv.23300","article-title":"Inter-Genotypic Recombinant Hepatitis C Virus Strains in Japan Noted by Discrepancies between Immunoassay and Sequencing","volume":"84","author":"Hoshino","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"198354","DOI":"10.1016\/j.virusres.2021.198354","article-title":"Complete Genome Analysis Identifies Recombinant Events and Positive Selection Sites of Hepatitis C Virus from Mainland China during 2010\u20132019","volume":"296","author":"Qi","year":"2021","journal-title":"Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1099\/vir.0.79984-0","article-title":"Full-Length Open Reading Frame of a Recombinant Hepatitis C Virus Strain from St Petersburg: Proposed Mechanism for Its Formation","volume":"85","author":"Kalinina","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.meegid.2016.12.001","article-title":"Recombination in Hepatitis C Virus Is Not Uncommon among People Who Inject Drugs in Kolkata, India","volume":"48","author":"Gupta","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1099\/vir.0.19472-0","article-title":"Evidence of Intratypic Recombination in Natural Populations of Hepatitis C Virus","volume":"85","author":"Colina","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7569","DOI":"10.1128\/JVI.00312-06","article-title":"Identification of a Naturally Occurring Recombinant Genotype 2\/6 Hepatitis C Virus","volume":"80","author":"Noppornpanth","year":"2006","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/jmv.20714","article-title":"A Natural Inter-Genotypic (2b\/1b) Recombinant of Hepatitis C Virus in the Philippines","volume":"78","author":"Kageyama","year":"2006","journal-title":"J. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1128\/JVI.02639-06","article-title":"New Natural Intergenotypic (2\/5) Recombinant of Hepatitis C Virus","volume":"81","author":"Claudinon","year":"2007","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1743-422X-3-53","article-title":"Evidence of Structural Genomic Region Recombination in Hepatitis C Virus","volume":"3","author":"Cristina","year":"2006","journal-title":"Virol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1872-034X.2007.00293.x","article-title":"Detection of Hepatitis C Virus Natural Recombinant RF1_2k\/1b Strain among Intravenous Drug Users in Uzbekistan","volume":"38","author":"Kurbanov","year":"2008","journal-title":"Hepatol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/1743-422X-6-203","article-title":"Evidence of Recombination in Hepatitis C Virus Populations Infecting a Hemophiliac Patient","volume":"6","author":"Moreno","year":"2009","journal-title":"Virol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1743-422X-3-87","article-title":"Evidence of Recombination in Quasispecies Populations of a Hepatitis C Virus Patient Undergoing Anti-Viral Therapy","volume":"3","author":"Moreno","year":"2006","journal-title":"Virol. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sentandreu, V., Jim\u00e9nez-Hern\u00e1ndez, N., Torres-Puente, M., Bracho, M.A., Valero, A., Gosalbes, M.J., Ortega, E., Moya, A., and Gonz\u00e1lez-Candelas, F. (2008). Evidence of Recombination in Intrapatient Populations of Hepatitis C Virus. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003239"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"831","DOI":"10.4254\/wjh.v7.i6.831","article-title":"Hepatitis C Virus Genetic Variability and Evolution","volume":"7","author":"Moratorio","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1365-2893.2010.01367.x","article-title":"Genetic Recombination of the Hepatitis C Virus: Clinical Implications","volume":"18","author":"Morel","year":"2011","journal-title":"J. Viral Hepat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e1876","DOI":"10.1097\/MD.0000000000001876","article-title":"Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV\/HCV Patients under Treatment with Peg-IFN\/Ribavirin","volume":"94","author":"Bagaglio","year":"2015","journal-title":"Medicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ijid.2017.12.016","article-title":"Hepatitis C Virus Deep Sequencing for Sub-Genotype Identification in Mixed Infections: A Real-Life Experience","volume":"67","author":"Figueruela","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9264","DOI":"10.1038\/s41598-019-42605-z","article-title":"Infection with Multiple Hepatitis C Virus Genotypes Detected Using Commercial Tests Should Be Confirmed Using next Generation Sequencing","volume":"9","author":"Chueca","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.meegid.2019.01.016","article-title":"A Systematic, Deep Sequencing-Based Methodology for Identification of Mixed-Genotype Hepatitis C Virus Infections","volume":"69","author":"Olmstead","year":"2019","journal-title":"Infect. Genet. Evol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1128\/JCM.43.8.3624-3629.2005","article-title":"Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Blood Donors from Southeast France","volume":"43","author":"Cantaloube","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: Improving the Sensitivity of Progressive Multiple Sequence Alignment through Sequence Weighting, Position-Specific Gap Penalties and Weight Matrix Choice","volume":"22","author":"Thompson","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/bioinformatics\/bth485","article-title":"The Los Alamos Hepatitis C Sequence Database","volume":"21","author":"Kuiken","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gky379","article-title":"The Galaxy Platform for Accessible, Reproducible and Collaborative Biomedical Analyses: 2018 Update","volume":"46","author":"Afgan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_48","unstructured":"Andrews, S. (2019, February 19). FastQC\u2014A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_50","unstructured":"Li, H. (2013). Aligning Sequence Reads, Clone Sequences and Assembly Contigs with BWA-MEM. arXiv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/bioinformatics\/btv566","article-title":"Qualimap 2: Advanced Multi-Sample Quality Control for High-Throughput Sequencing Data","volume":"32","author":"Okonechnikov","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map Format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1093\/bioinformatics\/btac287","article-title":"SimPlot++: A Python Application for Representing Sequence Similarity and Detecting Recombination","volume":"38","author":"Samson","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/JVI.73.1.152-160.1999","article-title":"Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination","volume":"73","author":"Lole","year":"1999","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"vev003","DOI":"10.1093\/ve\/vev003","article-title":"RDP4: Detection and Analysis of Recombination Patterns in Virus Genomes","volume":"1","author":"Martin","year":"2015","journal-title":"Virus Evol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/bioinformatics\/16.6.562","article-title":"RDP: Detection of Recombination amongst Aligned Sequences","volume":"16","author":"Martin","year":"2000","journal-title":"Bioinformatics. Oxf. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1006\/viro.1999.0056","article-title":"Possible Emergence of New Geminiviruses by Frequent Recombination","volume":"265","author":"Padidam","year":"1999","journal-title":"Virology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1089\/aid.2005.21.98","article-title":"A Modified Bootscan Algorithm for Automated Identification of Recombinant Sequences and Recombination Breakpoints","volume":"21","author":"Martin","year":"2005","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/bioinformatics\/16.7.573","article-title":"Sister-Scanning: A Monte Carlo Procedure for Assessing Signals in Recombinant Sequences","volume":"16","author":"Gibbs","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/oxfordjournals.molbev.a026121","article-title":"Phylogenetic Evidence for Recombination in Dengue Virus","volume":"16","author":"Holmes","year":"1999","journal-title":"Mol. Biol. Evol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/molbev\/msx263","article-title":"Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm","volume":"35","author":"Lam","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1743-422X-3-103","article-title":"Comparative Analysis of Hepatitis C Virus Phylogenies from Coding and Non-Coding Regions: The 5\u2032 Untranslated Region (UTR) Fails to Classify Subtypes","volume":"3","author":"Hraber","year":"2006","journal-title":"Virol. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.meegid.2015.03.021","article-title":"Epidemic History of Major Genotypes of Hepatitis C Virus in Uruguay","volume":"32","author":"Castells","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.virusres.2016.07.008","article-title":"Naturally Occurring NS3 Resistance-Associated Variants in Hepatitis C Virus Genotype 1: Their Relevance for Developing Countries","volume":"223","author":"Betancour","year":"2016","journal-title":"Virus Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Foster, G.R., and Reddy, K.R. (2020). Clinical Dilemmas in Viral Liver Disease, Wiley.","DOI":"10.1002\/9781119533481"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nrgastro.2015.36","article-title":"Mixed HCV Infection and Reinfection in People Who Inject Drugs\u2014Impact on Therapy","volume":"12","author":"Cunningham","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1086\/510858","article-title":"Hepatitis C Virus Coinfection and Superinfection","volume":"195","author":"Blackard","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Minosse, C., Giombini, E., Bartolini, B., Capobianchi, M., and Garbuglia, A. (2016). Ultra-Deep Sequencing Characterization of HCV Samples with Equivocal Typing Results Determined with a Commercial Assay. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101679"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"105252","DOI":"10.1016\/j.jcv.2022.105252","article-title":"Full-Genome next-Generation Sequencing of Hepatitis C Virus to Assess the Accuracy of Genotyping by the Commercial Assay LiPA and the Prevalence of Resistance-Associated Substitutions in a Belgian Cohort","volume":"155","author":"Christensen","year":"2022","journal-title":"J. Clin. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1365-2893.2005.00592.x","article-title":"Detection of Multiple Hepatitis C Virus Genotypes in a Cohort of Injecting Drug Users","volume":"12","author":"Bowden","year":"2005","journal-title":"J. Viral Hepat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/jvh.12849","article-title":"Prevalence of Mixed Genotype Hepatitis C Virus Infections in the UK as Determined by Genotype-specific PCR and Deep Sequencing","volume":"25","author":"McNaughton","year":"2018","journal-title":"J. Viral Hepat."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1111\/jgh.15546","article-title":"Pangenotypic Direct-acting Antiviral Agents for Mixed Genotype Hepatitis C Infection: A Real-world Effectiveness Analysis","volume":"36","author":"Ding","year":"2021","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yen, H.-H., Chen, Y.-Y., Lai, J.-H., Chen, H.-M., Yao, C.-T., Huang, S.-P., Liu, I.-L., Zeng, Y.-H., Yang, F.-C., and Siao, F.-Y. (2022). Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis. J. Clin. Med., 11.","DOI":"10.3390\/jcm11071853"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/jvh.13305","article-title":"Real-world Effectiveness of Glecaprevir\/Pibrentasvir and Ledipasvir\/Sofosbuvir for Mixed Genotype Hepatitis C Infection: A Multicenter Pooled Analysis in Taiwan","volume":"27","author":"Chiu","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_75","first-page":"1714","article-title":"Hepatitis C Guidance 2023 Update: American Association for the Study of Liver Diseases\u2013Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection","volume":"36","author":"Bhattacharya","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.jhep.2020.08.018","article-title":"EASL Recommendations on Treatment of Hepatitis C: Final Update of the Series\u2606","volume":"73","author":"Pawlotsky","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/molbev\/msn238","article-title":"Homologous Recombination as an Evolutionary Force in the Avian Influenza A Virus","volume":"26","author":"He","year":"2008","journal-title":"Mol. Biol. Evol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrmicro2614","article-title":"Why Do RNA Viruses Recombine?","volume":"9","author":"Holmes","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yuan, C., Liu, W., Wang, Y., Hou, J., Zhang, L., and Wang, G. (2017). Homologous Recombination Is a Force in the Evolution of Canine Distemper Virus. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175416"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/infdis\/jiy747","article-title":"High-Resolution Evolutionary Analysis of Within-Host Hepatitis C Virus Infection","volume":"219","author":"Raghwani","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Scheel, T.K.H., Galli, A., Li, Y.-P., Mikkelsen, L.S., Gottwein, J.M., and Bukh, J. (2013). Productive Homologous and Non-Homologous Recombination of Hepatitis C Virus in Cell Culture. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003228"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1182\/blood-2002-03-0818","article-title":"Differential Distribution and Internal Translation Efficiency of Hepatitis C Virus Quasispecies Present in Dendritic and Liver Cells","volume":"101","author":"Laporte","year":"2003","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10827","DOI":"10.1128\/JVI.74.22.10827-10833.2000","article-title":"Comparative Analysis of Translation Efficiencies of Hepatitis C Virus 5\u2032 Untranslated Regions among Intraindividual Quasispecies Present in Chronic Infection: Opposite Behaviors Depending on Cell Type","volume":"74","author":"Laporte","year":"2000","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1128\/JVI.78.10.5170-5183.2004","article-title":"Identification of Unique Hepatitis C Virus Quasispecies in the Central Nervous System and Comparative Analysis of Internal Translational Efficiency of Brain, Liver, and Serum Variants","volume":"78","author":"Forton","year":"2004","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"veab106","DOI":"10.1093\/ve\/veab106","article-title":"High Recombination Rate of Hepatitis C Virus Revealed by a Green Fluorescent Protein Reconstitution Cell System","volume":"8","author":"Galli","year":"2022","journal-title":"Virus Evol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/4\/560\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:22:56Z","timestamp":1760106176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/4\/560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":85,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["v16040560"],"URL":"https:\/\/doi.org\/10.3390\/v16040560","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]}}}