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Classification, Genetic Diversity and Global Distribution of Hepatitis C Virus (HCV) Genotypes and Subtypes

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Hepatitis C: Epidemiology, Prevention and Elimination

Abstract

Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus that belongs to the family Flaviviridae. HCV is characterized by extensive genetic heterogeneity and has been classified into genotypes, subtypes and recombinant forms (RFs). Revised HCV classification, based on phylogenetic analysis of a large number of nearly full-length sequences, has revealed the existence of seven major clades named genotypes 1–7. These genotypes have been further divided into 86 subtypes. Τhe distribution of genotypes, subtypes and RFs differs greatly with the geographic origin. Subtypes 1a, 1b, 2a and 3a are the most widely spread, being highly prevalent in high-income countries. They are known as the “epidemic subtypes”, and they have spread mostly as a result of blood and blood product transfusions, iatrogenic procedures and injecting drug use. Their global dissemination occurred before the identification of HCV in 1989. The remaining HCV subtypes are mostly prevalent in restricted geographic areas, and they are characterized as “endemic”. The genetic diversity of HCV is higher than that of the human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV), because HCV has been infecting humans for a longer time period compared to HIV-1 and does not have the overlapping reading frames present in HBV, which constrain the molecular evolution of HBV. HIV-1 group M is the result of a cross-species transmission event from chimpanzee that occurred approximately at the beginning of the twentieth century, suggesting a recent origin in humans. HBV, on the other hand, has co-expanded with modern humans for approximately 34,100 years, coinciding with the dispersal of modern non-African humans. Although HBV has been infecting humans for several 1000 years, the presence of overlapping reading frames in the viral genome decelerates its evolutionary rate making HBV less divergent than HCV.

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References

  1. Mizokami M, Orito E, Ohba K, Ikeo K, Lau JY, Gojobori T. Constrained evolution with respect to gene overlap of hepatitis B virus. J Mol Evol. 1997;44(Suppl 1):S83–90.

    Article  PubMed  Google Scholar 

  2. Korber B, Muldoon M, Theiler J, Gao F, Gupta R, Lapedes A, et al. Timing the ancestor of the HIV-1 pandemic strains. Science. 2000;288(5472):1789–96.

    Article  CAS  PubMed  Google Scholar 

  3. Paraskevis D, Magiorkinis G, Magiorkinis E, Ho SY, Belshaw R, Allain JP, et al. Dating the origin and dispersal of hepatitis B virus infection in humans and primates. Hepatology. 2013;57(3):908–16.

    Article  PubMed  Google Scholar 

  4. Paraskevis D, Angelis K, Magiorkinis G, Kostaki E, Ho SY, Hatzakis A. Dating the origin of hepatitis B virus reveals higher substitution rate and adaptation on the branch leading to F/H genotypes. Mol Phylogenet Evol. 2015;93:44–54.

    Article  PubMed  Google Scholar 

  5. Simmonds P, Bukh J, Combet C, Deleage G, Enomoto N, Feinstone S, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology. 2005;42(4):962–73.

    Article  CAS  PubMed  Google Scholar 

  6. Kuiken C, Combet C, Bukh J, Shin IT, Deleage G, Mizokami M, et al. A comprehensive system for consistent numbering of HCV sequences, proteins and epitopes. Hepatology. 2006;44(5):1355–61.

    Article  CAS  PubMed  Google Scholar 

  7. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59(1):318–27.

    Article  PubMed  Google Scholar 

  8. Simmonds P, Becher P, Bukh J, Gould EA, Meyers G, Monath T, et al. ICTV virus taxonomy profile: flaviviridae. J Gen Virol. 2017;98(1):2–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. https://talk.ictvonline.org/ictv_wikis/flaviviridae/w/sg_flavi/37/table-3-remaining-provisionally-assigned-hcv-subtypes-november-2014.

  10. Kuiken C, Hraber P, Thurmond J, Yusim K. The hepatitis C sequence database in Los Alamos. Nucleic Acids Res. 2008;36(Database issue):D512–6.

    CAS  PubMed  Google Scholar 

  11. Kuiken C, Yusim K, Boykin L, Richardson R. The Los Alamos hepatitis C sequence database. Bioinformatics. 2005;21(3):379–84.

    Article  CAS  PubMed  Google Scholar 

  12. Combet C, Penin F, Geourjon C, Deleage G. HCVDB: hepatitis C virus sequences database. Appl Bioinforma. 2004;3(4):237–40.

    Article  CAS  Google Scholar 

  13. Kalinina O, Norder H, Mukomolov S, Magnius LO. A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg J Virol. 2002;76(8):4034–43.

    Article  CAS  PubMed  Google Scholar 

  14. Kalinina O, Norder H, Magnius LO. Full-length open reading frame of a recombinant hepatitis C virus strain from St Petersburg: proposed mechanism for its formation. J Gen Virol. 2004;85(Pt 7):1853–7.

    Article  CAS  PubMed  Google Scholar 

  15. Noppornpanth S, Lien TX, Poovorawan Y, Smits SL, Osterhaus AD, Haagmans BL. Identification of a naturally occurring recombinant genotype 2/6 hepatitis C virus. J Virol. 2006;80(15):7569–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kageyama S, Agdamag DM, Alesna ET, Leano PS, Heredia AM, Abellanosa-Tac-An IP, et al. A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the Philippines. J Med Virol. 2006;78(11):1423–8.

    Article  CAS  PubMed  Google Scholar 

  17. Legrand-Abravanel F, Claudinon J, Nicot F, Dubois M, Chapuy-Regaud S, Sandres-Saune K, et al. New natural intergenotypic (2/5) recombinant of hepatitis C virus. J Virol. 2007;81(8):4357–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lee YM, Lin HJ, Chen YJ, Lee CM, Wang SF, Chang KY, et al. 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. J Med Virol. 2010;82(1):57–68.

    Article  PubMed  Google Scholar 

  19. Yokoyama K, Takahashi M, Nishizawa T, Nagashima S, Jirintai S, Yotsumoto S, et al. Identification and characterization of a natural inter-genotypic (2b/1b) recombinant hepatitis C virus in Japan. Arch Virol. 2011;156(9):1591–601.

    Article  CAS  PubMed  Google Scholar 

  20. Bhattacharya D, Accola MA, Ansari IH, Striker R, Rehrauer WM. Naturally occurring genotype 2b/1a hepatitis C virus in the United States. Virol J. 2011;8:458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hoshino H, Hino K, Miyakawa H, Takahashi K, Akbar SM, Mishiro S. Inter-genotypic recombinant hepatitis C virus strains in Japan noted by discrepancies between immunoassay and sequencing. J Med Virol. 2012;84(7):1018–24.

    Article  CAS  PubMed  Google Scholar 

  22. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77–87.

    Article  PubMed  Google Scholar 

  23. Smith DB, Pathirana S, Davidson F, Lawlor E, Power J, Yap PL, et al. The origin of hepatitis C virus genotypes. J Gen Virol. 1997;78(Pt 2):321–8.

    Article  CAS  PubMed  Google Scholar 

  24. Magiorkinis G, Magiorkinis E, Paraskevis D, Ho SY, Shapiro B, Pybus OG, et al. The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis. PLoS Med. 2009;6(12):e1000198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Pybus OG, Cochrane A, Holmes EC, Simmonds P. The hepatitis C virus epidemic among injecting drug users. Infect Genet Evol. 2005;5(2):131–9.

    Article  PubMed  Google Scholar 

  26. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244(4902):359–62.

    Article  CAS  PubMed  Google Scholar 

  27. Simmonds P. The origin and evolution of hepatitis viruses in humans. J Gen Virol. 2001;82(Pt 4):693–712.

    Article  CAS  PubMed  Google Scholar 

  28. Pybus OG, Barnes E, Taggart R, Lemey P, Markov PV, Rasachak B, et al. Genetic history of hepatitis C virus in East Asia. J Virol. 2009;83(2):1071–82.

    Article  CAS  PubMed  Google Scholar 

  29. Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017;2(3):161–76.

    Article  Google Scholar 

  30. Murray CJ, Ezzati M, Flaxman AD, Lim S, Lozano R, Michaud C, et al. GBD 2010: design, definitions, and metrics. Lancet. 2012;380(9859):2063–6.

    Article  PubMed  Google Scholar 

  31. Tanaka Y, Kurbanov F, Mano S, Orito E, Vargas V, Esteban JI, et al. Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology. 2006;130(3):703–14.

    Article  CAS  PubMed  Google Scholar 

  32. Morice Y, Cantaloube JF, Beaucourt S, Barbotte L, De Gendt S, Goncales FL, et al. Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users. J Med Virol. 2006;78(10):1296–303.

    Article  CAS  PubMed  Google Scholar 

  33. Guerra J, Garenne M, Mohamed MK, Fontanet A. HCV burden of infection in Egypt: results from a nationwide survey. J Viral Hepat. 2012;19(8):560–7.

    Article  CAS  PubMed  Google Scholar 

  34. Abdel-Ghaffar TY, Sira MM, El Naghi S. Hepatitis C genotype 4: the past, present, and future. World J Hepatol. 2015;7(28):2792–810.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355(9207):887–91.

    Article  CAS  PubMed  Google Scholar 

  36. Rao MR, Naficy AB, Darwish MA, Darwish NM, Schisterman E, Clemens JD, et al. Further evidence for association of hepatitis C infection with parenteral schistosomiasis treatment in Egypt. BMC Infect Dis. 2002;2:29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. El Sherbini A, Mohsen SA, Hasan W, Mostafa S, El Gohary K, Moneib A, et al. The peak impact of an Egyptian outbreak of hepatitis C virus: has it passed or has not yet occurred? Liver Int. 2007;27(6):876–7.

    Article  PubMed  Google Scholar 

  38. Habib M, Mohamed MK, Abdel-Aziz F, Magder LS, Abdel-Hamid M, Gamil F, et al. Hepatitis C virus infection in a community in the Nile Delta: risk factors for seropositivity. Hepatology. 2001;33(1):248–53.

    Article  CAS  PubMed  Google Scholar 

  39. Medhat A, Shehata M, Magder LS, Mikhail N, Abdel-Baki L, Nafeh M, et al. Hepatitis c in a community in Upper Egypt: risk factors for infection. Am J Trop Med Hyg. 2002;66(5):633–8.

    Article  PubMed  Google Scholar 

  40. Arafa N, El Hoseiny M, Rekacewicz C, Bakr I, El-Kafrawy S, El Daly M, et al. Changing pattern of hepatitis C virus spread in rural areas of Egypt. J Hepatol. 2005;43(3):418–24.

    Article  PubMed  Google Scholar 

  41. Darwish MA, Faris R, Darwish N, Shouman A, Gadallah M, El-Sharkawy MS, et al. Hepatitis c and cirrhotic liver disease in the Nile delta of Egypt: a community-based study. Am J Trop Med Hyg. 2001;64(3-4):147–53.

    Article  CAS  PubMed  Google Scholar 

  42. Katsoulidou A, Sypsa V, Tassopoulos NC, Boletis J, Karafoulidou A, Ketikoglou I, et al. Molecular epidemiology of hepatitis C virus (HCV) in Greece: temporal trends in HCV genotype-specific incidence and molecular characterization of genotype 4 isolates. J Viral Hepat. 2006;13(1):19–27.

    Article  CAS  PubMed  Google Scholar 

  43. Henquell C, Guglielmini J, Verbeeck J, Mahul A, Thibault V, Lebray P, et al. Evolutionary history of hepatitis C virus genotype 5a in France, a multicenter ANRS study. Infect Genet Evol. 2011;11(2):496–503.

    Article  PubMed  Google Scholar 

  44. Stumpf MP, Pybus OG. Genetic diversity and models of viral evolution for the hepatitis C virus. FEMS Microbiol Lett. 2002;214(2):143–52.

    Article  CAS  PubMed  Google Scholar 

  45. Murphy DG, Sablon E, Chamberland J, Fournier E, Dandavino R, Tremblay CL. Hepatitis C virus genotype 7, a new genotype originating from central Africa. J Clin Microbiol. 2015;53(3):967–72.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Salmona M, Caporossi A, Simmonds P, Thelu MA, Fusillier K, Mercier-Delarue S, et al. First next-generation sequencing full-genome characterization of a hepatitis C virus genotype 7 divergent subtype. Clin Microbiol Infect. 2016;22(11):947 e1-e8.

    Article  CAS  Google Scholar 

  47. Kramvis A. Genotypes and genetic variability of hepatitis B virus. Intervirology. 2014;57(3-4):141–50.

    Article  PubMed  Google Scholar 

  48. Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47(6):289–309.

    Article  PubMed  Google Scholar 

  49. Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F. Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol. 2014;20(23):7152–68.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kramvis A, Kew M, Francois G. Hepatitis B virus genotypes. Vaccine. 2005;23(19):2409–23.

    Article  CAS  PubMed  Google Scholar 

  51. Foley BT, Leitner T, Paraskevis D, Peeters M. Primate immunodeficiency virus classification and nomenclature: review. Infect Genet Evol. 2016;46:150–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hauri AM, Armstrong GL, Hutin YJ. The global burden of disease attributable to contaminated injections given in health care settings. Int J STD AIDS. 2004;15(1):7–16.

    Article  PubMed  Google Scholar 

  53. Sharp PM, Bailes E, Chaudhuri RR, Rodenburg CM, Santiago MO, Hahn BH. The origins of acquired immune deficiency syndrome viruses: where and when? Philos Trans R Soc Lond Ser B Biol Sci. 2001;356(1410):867–76.

    Article  CAS  Google Scholar 

  54. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature. 1999;397(6718):436–41.

    Article  CAS  PubMed  Google Scholar 

  55. Tebit DM, Arts EJ. Tracking a century of global expansion and evolution of HIV to drive understanding and to combat disease. Lancet Infect Dis. 2011;11(1):45–56.

    Article  PubMed  Google Scholar 

  56. Takebe Y, Uenishi R, Li X. Global molecular epidemiology of HIV: understanding the genesis of AIDS pandemic. Adv Pharmacol. 2008;56:1–25.

    Article  PubMed  CAS  Google Scholar 

  57. Magiorkinis G, Angelis K, Mamais I, Katzourakis A, Hatzakis A, Albert J, et al. The global spread of HIV-1 subtype B epidemic. Infect Genet Evol. 2016;46:169–79.

    Article  PubMed  PubMed Central  Google Scholar 

  58. McCutchan FE, Hoelscher M, Tovanabutra S, Piyasirisilp S, Sanders-Buell E, Ramos G, et al. In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months postinfection. J Virol. 2005;79(18):11693–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Dimitrios Paraskevis, Evangelia Georgia Kostaki & Gkikas Magiorkinis

  2. Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Anna Kramvis

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  1. Dimitrios Paraskevis
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  2. Evangelia Georgia Kostaki
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  4. Gkikas Magiorkinis
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Correspondence to Dimitrios Paraskevis .

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  1. Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens Medical School, Athens, Greece

    Angelos Hatzakis

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Paraskevis, D., Kostaki, E.G., Kramvis, A., Magiorkinis, G. (2021). Classification, Genetic Diversity and Global Distribution of Hepatitis C Virus (HCV) Genotypes and Subtypes. In: Hatzakis, A. (eds) Hepatitis C: Epidemiology, Prevention and Elimination . Springer, Cham. https://doi.org/10.1007/978-3-030-64649-3_3

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