1887

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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2012-06-01
2019-10-22
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References

  1. Abid K., Quadri R., Veuthey A. L., Hadengue A., Negro F.. ( 2000;). A novel hepatitis C virus (HCV) subtype from Somalia and its classification into HCV clade 3. . J Gen Virol 81:, 1485–1493.[PubMed]
    [Google Scholar]
  2. Abid K., Pazienza V., de Gottardi A., Rubbia-Brandt L., Conne B., Pugnale P., Rossi C., Mangia A., Negro F.. ( 2005;). An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation. . J Hepatol 42:, 744–751. [CrossRef][PubMed]
    [Google Scholar]
  3. Candotti D., Temple J., Sarkodie F., Allain J. P.. ( 2003;). Frequent recovery and broad genotype 2 diversity characterize hepatitis C virus infection in Ghana, West Africa. . J Virol 77:, 7914–7923. [CrossRef][PubMed]
    [Google Scholar]
  4. Cantaloube J. F., Biagini P., Attoui H., Gallian P., de Micco P., de Lamballerie X.. ( 2003;). Evolution of hepatitis C virus in blood donors and their respective recipients. . J Gen Virol 84:, 441–446. [CrossRef][PubMed]
    [Google Scholar]
  5. Cantaloube J. F., Gallian P., Laperche S., Elghouzzi M. H., Piquet Y., Bouchardeau F., Jordier F., Biagini P., Attoui H., de Micco P.. ( 2008;). Molecular characterization of genotype 2 and 4 hepatitis C virus isolates in French blood donors. . J Med Virol 80:, 1732–1739. [CrossRef][PubMed]
    [Google Scholar]
  6. Colina R., Casane D., Vasquez S., García-Aguirre L., Chunga A., Romero H., Khan B., Cristina J.. ( 2004;). Evidence of intratypic recombination in natural populations of hepatitis C virus. . J Gen Virol 85:, 31–37. [CrossRef][PubMed]
    [Google Scholar]
  7. Drummond A. J., Rambaut A.. ( 2007;). beast: Bayesian evolutionary analysis by sampling trees. . BMC Evol Biol 7:, 214. [CrossRef][PubMed]
    [Google Scholar]
  8. Enomoto N., Sato C.. ( 1995;). Clinical relevance of hepatitis C virus quasispecies. . J Viral Hepat 2:, 267–272. [CrossRef][PubMed]
    [Google Scholar]
  9. Feld J. J., Hoofnagle J. H.. ( 2005;). Mechanism of action of interferon and ribavirin in treatment of hepatitis C. . Nature 436:, 967–972. [CrossRef][PubMed]
    [Google Scholar]
  10. Gale M. Jr, Katze M. G.. ( 1998;). Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. . Pharmacol Ther 78:, 29–46. [CrossRef][PubMed]
    [Google Scholar]
  11. Gale M. J. Jr, Korth M. J., Katze M. G.. ( 1998;). Repression of the PKR protein kinase by the hepatitis C virus NS5A protein: a potential mechanism of interferon resistance. . Clin Diagn Virol 10:, 157–162. [CrossRef][PubMed]
    [Google Scholar]
  12. Hall T. A.. ( 1999;). BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser. 41:, 95–98. [CrossRef][PubMed]
    [Google Scholar]
  13. Hasegawa M., Kishino H., Yano T.. ( 1985;). Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. . J Mol Evol 22:, 160–174. [CrossRef][PubMed]
    [Google Scholar]
  14. Holland P. V., Barrera J. M., Ercilla M. G., Yoshida C. F., Wang Y., de Olim G. A., Betlach B., Kuramoto K., Okamoto H.. ( 1996;). Genotyping hepatitis C virus isolates from Spain, Brazil, China, and Macau by a simplified PCR method. . J Clin Microbiol 34:, 2372–2378.[PubMed]
    [Google Scholar]
  15. Hourioux C., Patient R., Morin A., Blanchard E., Moreau A., Trassard S., Giraudeau B., Roingeard P.. ( 2007;). The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model. . Gut 56:, 1302–1308. [CrossRef][PubMed]
    [Google Scholar]
  16. Jackel-Cram C., Babiuk L. A., Liu Q.. ( 2007;). Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. . J Hepatol 46:, 999–1008. [CrossRef][PubMed]
    [Google Scholar]
  17. Jeannel D., Fretz C., Traore Y., Kohdjo N., Bigot A., Pê Gamy E., Jourdan G., Kourouma K., Maertens G.. & other authors ( 1998;). Evidence for high genetic diversity and long-term endemicity of hepatitis C virus genotypes 1 and 2 in West Africa. . J Med Virol 55:, 92–97. [CrossRef][PubMed]
    [Google Scholar]
  18. Kalinina O., Norder H., Mukomolov S., Magnius L. O.. ( 2002;). A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg. . J Virol 76:, 4034–4043. [CrossRef][PubMed]
    [Google Scholar]
  19. Kalinina O., Norder H., Magnius L. O.. ( 2004;). Full-length open reading frame of a recombinant hepatitis C virus strain from St Petersburg: proposed mechanism for its formation. . J Gen Virol 85:, 1853–1857. [CrossRef][PubMed]
    [Google Scholar]
  20. Kwok S., Higuchi R.. ( 1989;). Avoiding false positives with PCR. . Nature 339:, 237–238. [CrossRef][PubMed]
    [Google Scholar]
  21. Le Pogam S., Dubois F., Christen R., Raby C., Cavicchini A., Goudeau A.. ( 1998;). Comparison of DNA enzyme immunoassay and line probe assays (Inno-LiPA HCV I and II) for hepatitis C virus genotyping. . J Clin Microbiol 36:, 1461–1463.[PubMed]
    [Google Scholar]
  22. Lee Y. M., Lin H. J., Chen Y. J., Lee C. M., Wang S. F., Chang K. Y., Chen T. L., Liu H. F., Chen Y. M.. ( 2010;). 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 82:, 57–68. [CrossRef][PubMed]
    [Google Scholar]
  23. Legrand-Abravanel F., Claudinon J., Nicot F., Dubois M., Chapuy-Regaud S., Sandres-Saune K., Pasquier C., Izopet J.. ( 2007;). New natural intergenotypic (2/5) recombinant of hepatitis C virus. . J Virol 81:, 4357–4362. [CrossRef][PubMed]
    [Google Scholar]
  24. Li C., Fu Y., Lu L., Ji W., Yu J., Hagedorn C. H., Zhang L.. ( 2006;). Complete genomic sequences for hepatitis C virus subtypes 6e and 6g isolated from Chinese patients with injection drug use and HIV-1 co-infection. . J Med Virol 78:, 1061–1069. [CrossRef][PubMed]
    [Google Scholar]
  25. Li C., Lu L., Wu X., Wang C., Bennett P., Lu T., Murphy D.. ( 2009;). Complete genomic sequences for hepatitis C virus subtypes 4b, 4c, 4d, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r and 4t. . J Gen Virol 90:, 1820–1826. [CrossRef][PubMed]
    [Google Scholar]
  26. Lu L., Li C., Fu Y., Thaikruea L., Thongswat S., Maneekarn N., Apichartpiyakul C., Hotta H., Okamoto H.. & other authors ( 2007;). Complete genomes for hepatitis C virus subtypes 6f, 6i, 6j and 6m: viral genetic diversity among Thai blood donors and infected spouses. . J Gen Virol 88:, 1505–1518. [CrossRef][PubMed]
    [Google Scholar]
  27. Manns M. P., McHutchison J. G., Gordon S. C., Rustgi V. K., Shiffman M., Reindollar R., Goodman Z. D., Koury K., Ling M., Albrecht J. K.. ( 2001;). Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. . Lancet 358:, 958–965. [CrossRef][PubMed]
    [Google Scholar]
  28. Manns M. P., Wedemeyer H., Cornberg M.. ( 2006;). Treating viral hepatitis C: efficacy, side effects, and complications. . Gut 55:, 1350–1359. [CrossRef][PubMed]
    [Google Scholar]
  29. Markov P. V., Pepin J., Frost E., Deslandes S., Labbé A. C., Pybus O. G.. ( 2009;). Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa. . J Gen Virol 90:, 2086–2096. [CrossRef][PubMed]
    [Google Scholar]
  30. Martial J., Morice Y., Abel S., Cabié A., Rat C., Lombard F., Edouard A., Pierre-Louis S., Garsaud P.. & other authors ( 2004;). Hepatitis C virus (HCV) genotypes in the Caribbean island of Martinique: evidence for a large radiation of HCV-2 and for a recent introduction from Europe of HCV-4. . J Clin Microbiol 42:, 784–791. [CrossRef][PubMed]
    [Google Scholar]
  31. Martin D. P., Williamson C., Posada D.. ( 2005;). rdp2: recombination detection and analysis from sequence alignments. . Bioinformatics 21:, 260–262. [CrossRef][PubMed]
    [Google Scholar]
  32. Mellor J., Holmes E. C., Jarvis L. M., Yap P. L., Simmonds P..The International HCV Collaborative Study Group ( 1995;). Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification. . J Gen Virol 76:, 2493–2507. [CrossRef][PubMed]
    [Google Scholar]
  33. Murphy D. G., Willems B., Deschênes M., Hilzenrat N., Mousseau R., Sabbah S.. ( 2007;). Use of sequence analysis of the NS5B region for routine genotyping of hepatitis C virus with reference to C/E1 and 5′ untranslated region sequences. . J Clin Microbiol 45:, 1102–1112. [CrossRef][PubMed]
    [Google Scholar]
  34. Nakao H., Okamoto H., Tokita H., Inoue T., Iizuka H., Pozzato G., Mishiro S.. ( 1996;). Full-length genomic sequence of a hepatitis C virus genotype 2c isolate (BEBE1) and the 2c-specific PCR primers. . Arch Virol 141:, 701–704. [CrossRef][PubMed]
    [Google Scholar]
  35. Ndjomou J., Pybus O. G., Matz B.. ( 2003;). Phylogenetic analysis of hepatitis C virus isolates indicates a unique pattern of endemic infection in Cameroon. . J Gen Virol 84:, 2333–2341. [CrossRef][PubMed]
    [Google Scholar]
  36. Negro F.. ( 2006;). Mechanisms and significance of liver steatosis in hepatitis C virus infection. . World J Gastroenterol 12:, 6756–6765.[PubMed]
    [Google Scholar]
  37. Njouom R., Pasquier C., Ayouba A., Sandres-Sauné K., Mfoupouendoun J., Mony Lobe M., Tene G., Thonnon J., Izopet J., Nerrienet E.. ( 2003a;). Hepatitis C virus infection among pregnant women in Yaounde, Cameroon: prevalence, viremia, and genotypes. . J Med Virol 69:, 384–390. [CrossRef][PubMed]
    [Google Scholar]
  38. Njouom R., Pasquier C., Ayouba A., Gessain A., Froment A., Mfoupouendoun J., Pouillot R., Dubois M., Sandres-Sauné K.. & other authors ( 2003b;). High rate of hepatitis C virus infection and predominance of genotype 4 among elderly inhabitants of a remote village of the rain forest of South Cameroon. . J Med Virol 71:, 219–225. [CrossRef][PubMed]
    [Google Scholar]
  39. Njouom R., Pasquier C., Ayouba A., Tejiokem M. C., Vessiere A., Mfoupouendoun J., Tene G., Eteki N., Lobe M. M.. & other authors ( 2005;). Low risk of mother-to-child transmission of hepatitis C virus in Yaounde, Cameroon: the ANRS 1262 study. . Am J Trop Med Hyg 73:, 460–466.[PubMed]
    [Google Scholar]
  40. Noppornpanth S., Lien T. X., Poovorawan Y., Smits S. L., Osterhaus A. D., Haagmans B. L.. ( 2006;). Identification of a naturally occurring recombinant genotype 2/6 hepatitis C virus. . J Virol 80:, 7569–7577. [CrossRef][PubMed]
    [Google Scholar]
  41. Pasquier C., Njouom R., Ayouba A., Dubois M., Sartre M. T., Vessière A., Timba I., Thonnon J., Izopet J., Nerrienet E.. ( 2005;). Distribution and heterogeneity of hepatitis C genotypes in hepatitis patients in Cameroon. . J Med Virol 77:, 390–398. [CrossRef][PubMed]
    [Google Scholar]
  42. Pearlman B. L.. ( 2004;). Hepatitis C infection: a clinical review. . South Med J 97:, 364–373, quiz 374. [CrossRef][PubMed]
    [Google Scholar]
  43. Posada D., Crandall K. A.. ( 1998;). modeltest: testing the model of DNA substitution. . Bioinformatics 14:, 817–818. [CrossRef][PubMed]
    [Google Scholar]
  44. Pouillot R., Lachenal G., Pybus O. G., Rousset D., Njouom R.. ( 2008;). Variable epidemic histories of hepatitis C virus genotype 2 infection in West Africa and Cameroon. . Infect Genet Evol 8:, 676–681. [CrossRef][PubMed]
    [Google Scholar]
  45. Pybus O. G., Markov P. V., Wu A., Tatem A. J.. ( 2007;). Investigating the endemic transmission of the hepatitis C virus. . Int J Parasitol 37:, 839–849. [CrossRef][PubMed]
    [Google Scholar]
  46. Qu D., Hantz O., Gouy M., Vitvitski L., Li J. S., Berby F., Tong S. P., Trépo C.. ( 1994;). Heterogeneity of hepatitis C virus genotypes in France. . J Gen Virol 75:, 1063–1070. [CrossRef][PubMed]
    [Google Scholar]
  47. Rubbia-Brandt L., Quadri R., Abid K., Giostra E., Malé P. J., Mentha G., Spahr L., Zarski J. P., Borisch B.. & other authors ( 2000;). Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. . J Hepatol 33:, 106–115. [CrossRef][PubMed]
    [Google Scholar]
  48. Ruggieri A., Argentini C., Kouruma F., Chionne P., D’Ugo E., Spada E., Dettori S., Sabbatani S., Rapicetta M.. ( 1996;). Heterogeneity of hepatitis C virus genotype 2 variants in West Central Africa (Guinea Conakry). . J Gen Virol 77:, 2073–2076. [CrossRef][PubMed]
    [Google Scholar]
  49. Sakai A., Kaneko S., Honda M., Matsushita E., Kobayashi K.. ( 1999;). Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis. . Hepatology 30:, 556–561. [CrossRef][PubMed]
    [Google Scholar]
  50. Sakai A., Claire M. S., Faulk K., Govindarajan S., Emerson S. U., Purcell R. H., Bukh J.. ( 2003;). The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci U S A. 100:, 11646–11651. [CrossRef][PubMed]
    [Google Scholar]
  51. Samokhvalov E. I., Hijikata M., Gylka R. I., Lvov D. K., Mishiro S.. ( 2000;). Full-genome nucleotide sequence of a hepatitis C virus variant (isolate name VAT96) representing a new subtype within the genotype 2 (arbitrarily 2k). . Virus Genes 20:, 183–187. [CrossRef][PubMed]
    [Google Scholar]
  52. Simmonds P., Bukh J., Combet C., Deléage G., Enomoto N., Feinstone S., Halfon P., Inchauspé G., Kuiken C.. & other authors ( 2005;). Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. . Hepatology 42:, 962–973. [CrossRef][PubMed]
    [Google Scholar]
  53. Stuyver L., van Arnhem W., Wyseur A., Hernandez F., Delaporte E., Maertens G.. ( 1994;). Classification of hepatitis C viruses based on phylogenetic analysis of the envelope 1 and nonstructural 5B regions and identification of five additional subtypes. . Proc Natl Acad Sci U S A 91:, 10134–10138. [CrossRef][PubMed]
    [Google Scholar]
  54. Tamura K., Dudley J., Nei M., Kumar S.. ( 2007;). mega4: Molecular Evolutionary Genetics Analysis (mega) software version 4.0. . Mol Biol Evol 24:, 1596–1599. [CrossRef][PubMed]
    [Google Scholar]
  55. Tamura K., Peterson D., Peterson N., Stecher J., Nei M., Kumar S.. ( 2011;). MEGAS: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 28:, 2731–2739. [CrossRef][PubMed]
    [Google Scholar]
  56. Taylor D. R., Shi S. T., Romano P. R., Barber G. N., Lai M. M.. ( 1999;). Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. . Science 285:, 107–110. [CrossRef][PubMed]
    [Google Scholar]
  57. Thomas F., Nicot F., Sandres-Sauné K., Dubois M., Legrand-Abravanel F., Alric L., Peron J. M., Pasquier C., Izopet J.. ( 2007;). Genetic diversity of HCV genotype 2 strains in south western France. . J Med Virol 79:, 26–34. [CrossRef][PubMed]
    [Google Scholar]
  58. Tokita H., Okamoto H., Iizuka H., Kishimoto J., Tsuda F., Lesmana L. A., Miyakawa Y., Mayumi M.. ( 1996;). Hepatitis C virus variants from Jakarta, Indonesia classifiable into novel genotypes in the second (2e and 2f), tenth (10a) and eleventh (11a) genetic groups. . J Gen Virol 77:, 293–301. [CrossRef][PubMed]
    [Google Scholar]
  59. Utama A., Tania N. P., Dhenni R., Gani R. A., Hasan I., Sanityoso A., Lelosutan S. A., Martamala R., Lesmana L. A.. & other authors ( 2010;). Genotype diversity of hepatitis C virus (HCV) in HCV-associated liver disease patients in Indonesia. . Liver Int 30:, 1152–1160. [CrossRef][PubMed]
    [Google Scholar]
  60. Wansbrough-Jones M. H., Frimpong E., Cant B., Harris K., Evans M. R., Teo C. G.. ( 1998;). Prevalence and genotype of hepatitis C virus infection in pregnant women and blood donors in Ghana. . Trans R Soc Trop Med Hyg 92:, 496–499. [CrossRef][PubMed]
    [Google Scholar]
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