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Nomenclature and Numbering of the Hepatitis C Virus

  • Protocol
Hepatitis C

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 510))

Abstract

International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. Consistency in numbering is also increasingly required for functional and clinical studies of HCV. For example, an unambiguous method for referring to amino acid substitutions at specific positions in NS3 and NS5B coding sequences associated with resistance to specific HCV inhibitors is essential in the investigation of antiviral treatment. Inconsistent and inaccurate numbering of locations in DNA and protein sequences is becoming a problem in the HCV scientific literature.

A group of experts in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and the Los Alamos National Laboratory (United States), convened to reexamine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. They also discussed how HCV sequence databases could introduce and facilitate a standardized numbering system for HCV nucleotides, proteins, and epitopes.

A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name reassignments to create consistency in nomenclature. A consensus proposal was drawn up for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. The proposed numbering system was adapted from the Los Alamos HIV database, with elements from the hepatitis B virus numbering system. The system comprises both nucleotides and amino acid sequences and epitopes, and uses the full-length genome sequence of isolate H77 (accession number AF009606) as a reference. It includes a method for numbering insertions and deletions relative to this reference sequence.

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References

  1. Simmonds, P., Holmes, E. C., Cha, T. A., Chan, S. W., McOmish, F., Irvine, B., et al. (1993) Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J. Gen. Virol. 74, 2391–2399.

    Article  CAS  PubMed  Google Scholar 

  2. Cha, T. A., Beall, E., Irvine, B., Kolberg, J., Chien, D., Kuo, G., et al. (1992) At least five related, but distinct, hepatitis C viral genotypes exist. Proc. Natl. Acad. Sci. USA 89, 7144–7148.

    Article  CAS  PubMed  Google Scholar 

  3. Simmonds, P., Bukh, J., Combet, C., Deléage, G., Enomoto, N., Feinstone, S., et al. (2005) Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42, 962–973.

    Article  CAS  PubMed  Google Scholar 

  4. Robertson, B., Myers, G., Howard, C., Brettin, T., Bukh, J., Gaschen, B., et al. (1998) Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. International Committee on Virus Taxonomy. Arch. Virol. 143, 2493–2503.

    Article  CAS  PubMed  Google Scholar 

  5. Simmonds, P., Holmes, E. C., Cha, T. A., Chan, S. W., McOmish, F., Irvine, B., et al. (1994) Identification of genotypes of hepatitis C virus by sequence comparisons in the core, E1 and NS-5 regions. J. Gen. Virol. 75, 1053–1061.

    Article  CAS  PubMed  Google Scholar 

  6. Jeannel, D., Fretz, C., Traore, Y., Kohdjo, N., Bigot, A., Pê Gamy, E., et al. (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.

    Article  CAS  PubMed  Google Scholar 

  7. Ruggieri, A., Argentini, C., Kouruma, F., Chionne, P., D’Ugo, E., Spada, E., et al. (1996) Heterogeneity of hepatitis C virus genotype 2 variants in West Central Africa (Guinea Conakry). J. Gen. Virol. 77, 2073–2076.

    Article  CAS  PubMed  Google Scholar 

  8. Candotti, D., Temple, J., Sarkodie, F., and 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.

    Article  CAS  PubMed  Google Scholar 

  9. Mellor, J., Holmes, E. C., Jarvis, L. M., Yap, P. L., and Simmonds, P. (1995) Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification. The International HCV Collaborative Study Group. J. Gen. Virol. 76, 2493–2507.

    Article  CAS  PubMed  Google Scholar 

  10. Ndjomou, J., Kupfer, B., Kochan, B., Zekeng, L., Kaptue, L., and Matz, B. (2002) Hepatitis C virus infection and genotypes among human immunodeficiency virus high-risk groups in Cameroon. J. Med. Virol. 66, 179–186.

    Article  PubMed  Google Scholar 

  11. Fretz, C., Jeannel, D., Stuyver, L., Hervé, V., Lunel, F., Boudifa, A., et al. (1995) HCV infection in a rural population of the Central African Republic (CAR): evidence for three additional subtypes of genotype 4. J. Med. Virol. 47, 435–437.

    Article  CAS  PubMed  Google Scholar 

  12. Tokita, H., Shrestha, S. M., Okamoto, H., Sakamoto, M., Horikita, M., Iizuka, H., et al. (1994) Hepatitis C virus variants from Nepal with novel genotypes and their classification into the third major group. J. Gen. Virol. 75, 931–936.

    Article  CAS  PubMed  Google Scholar 

  13. Tokita, H., Okamoto, H., Luengrojanakul, P., Vareesangthip, K., Chainuvati, T., Iizuka, H., et al. (1995) Hepatitis C virus variants from Thailand classifiable into five novel genotypes in the sixth (6b), seventh (7c, 7d) and ninth (9b, 9c) major genetic groups. J. Gen. Virol. 76, 2329–2335.

    Article  CAS  PubMed  Google Scholar 

  14. Tokita, H., Okamoto, H., Tsuda, F., Song, P., Nakata, S., Chosa, T., et al. (1994) Hepatitis C virus variants from Vietnam are classifiable into the seventh, eighth, and ninth major genetic groups. Proc. Natl. Acad. Sci. USA 91, 11022–11026.

    Article  CAS  PubMed  Google Scholar 

  15. Marsh, M., Helenius, A., Pybus, O. G., Charleston, M. A., Gupta, S., Rambaut, A., et al. (2001) The epidemic behavior of the hepatitis C virus. Science 292, 2323–2325.

    Article  Google Scholar 

  16. Simmonds, P. The origin and evolution of hepatitis viruses in humans. J. Gen. Virol. 82, 693–712.

    Google Scholar 

  17. Cochrane, A., Searle, B., Hardie, A., Robertson, R., Delahooke, T., Cameron, S., et al. (2002) A genetic analysis of hepatitis C virus transmission between injection drug users. J. Infect. Dis. 186, 1212–1221.

    Article  CAS  PubMed  Google Scholar 

  18. Legrand-Abravanel, F., Claudinon, J., Nicot, F., Dubois, M., Chapuy-Regaud, S., Sandres-Saune, K., et al. (2007) New natural intergenotypic (2/5) recombinant of hepatitis C virus. J Virol. 81, 4357–4362.

    Article  CAS  PubMed  Google Scholar 

  19. Tokita, H., Shrestha, S. M., Okamoto, H., Sakamoto, M., Horikita, M., Iizuka, H., et al. (2006) Serendipitous identification of natural intergenotypic recombinants of hepatitis C in Ireland. Virol. J. 3, 95–95.

    Article  Google Scholar 

  20. Kageyama, S., Agdamag, D. M., Alesna, E. T., Leaño, P. S., Heredia, A. M. L., Abellanosa-Tac-An, I. P., et al. (2006) A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the Philippines. J. Med. Virol. 78, 1423–1428.

    Article  CAS  PubMed  Google Scholar 

  21. Colina, R., Casane, D., Vasquez, S., García-Aguirre, L., Chunga, A., Romero, H., et al. (2004) Evidence of intratypic recombination in natural populations of hepatitis C virus. J. Gen. Virol. 85, 31–37.

    Article  CAS  PubMed  Google Scholar 

  22. Kalinina, O., Norder, H., Mukomolov, S., and Magnius, L. O. (2002) A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg. J. Virol. 76, 4034–4043.

    Article  CAS  PubMed  Google Scholar 

  23. Noppornpanth, S., Lien, T. X., Poovorawan, Y., Smits, S. L., Osterhaus, A. D. M. E., and Haagmans, B. L. (2006) Identification of a naturally occurring recombinant genotype 2/6 hepatitis C virus. J. Virol. 80, 7569–7577.

    Article  CAS  PubMed  Google Scholar 

  24. Hnatyszyn, H. J. (2005) Chronic hepatitis C and genotyping: the clinical significance of determining HCV genotypes. Antiviral Ther. 10, 1–11.

    CAS  Google Scholar 

  25. Stuyver, L., Rossau, R., Wyseur, A., Duhamel, M., Vanderborght, B., Van Heuverswyn, H., et al. (1993) Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J. Gen. Virol. 74, 1093–1102.

    Article  CAS  PubMed  Google Scholar 

  26. Davidson, F., Simmonds, P., Ferguson, J. C., Jarvis, L. M., Dow, B. C., Follett, E. A., et al. (1995) Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5′ non-coding region. J. Gen. Virol. 76, 1197–1204.

    Article  CAS  PubMed  Google Scholar 

  27. Ross, R. S., Viazov, S. O., Holtzer, C. D., Beyou, A., Monnet, A., Mazure, C., et al. (2000) Genotyping of hepatitis C virus isolates using CLIP sequencing. J. Clin. Microbiol. 38, 3581–3584.

    CAS  PubMed  Google Scholar 

  28. Simmonds, P., Rose, K. A., Graham, S., Chan, S. W., McOmish, F., Dow, B. C., et al. (1993) Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV): use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3. J. Clin. Microbiol. 31, 1493–1503.

    CAS  PubMed  Google Scholar 

  29. Lau, J. Y., Mizokami, M., Kolberg, J. A., Davis, G. L., Prescott, L. E., Ohno, T., et al. (1995) Application of six hepatitis C virus genotyping systems to sera from chronic hepatitis C patients in the United States. J. Infect. Dis. 171, 281–289.

    CAS  PubMed  Google Scholar 

  30. Zheng, X., Pang, M., Chan, A., Roberto, A., Warner, D., and Yen-Lieberman, B. (2003) Direct comparison of hepatitis C virus genotypes tested by INNO-LiPA HCV II and TRUGENE HCV genotyping methods. J. Clin. Virol. 28, 214–216.

    Article  CAS  PubMed  Google Scholar 

  31. Gault, E., Soussan, P., Morice, Y., Sanders, L., Berrada, A., Rogers, B., et al. (2003) Evaluation of a new serotyping assay for detection of anti-hepatitis C virus type-specific antibodies in serum samples. J. Clin. Microbiol. 41, 2084–2087.

    Article  CAS  PubMed  Google Scholar 

  32. Mellor, J., Walsh, E. A., Prescott, L. E., Jarvis, L. M., Davidson, F., Yap, P. L., et al. Survey of type 6 group variants of hepatitis C virus in Southeast Asia by using a core-based genotyping assay. J. Clin. Microbiol. 34, 417–423.

    Google Scholar 

  33. Bukh, J., Purcell, R. H., and Miller, R. H. (1993) At least 12 genotypes of hepatitis C virus predicted by sequence analysis of the putative E1 gene of isolates collected worldwide. Proc. Natl. Acad. Sci. USA 90, 8234–8238.

    Article  CAS  PubMed  Google Scholar 

  34. Samokhvalov, E. I., Hijikata, M., Gylka, R. I.,Lvov, D. K., and 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 2 k). Virus Genes 20, 183–187.

    Article  CAS  PubMed  Google Scholar 

  35. Tokita, H., Okamoto, H,, Iizuka, H., Kishimoto, J., Tsuda, F., Lesmana, L. A., et al. (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.

    Article  CAS  PubMed  Google Scholar 

  36. Depla, E., Maertens, G., De Nys, K., Blockx, H., Van Doorn, L. J., Quint, W., et al. (2003) A putative new clade 7 of hepatitis C virus containing at least one type and two subtypes, in 10th International Meeting on Hepatitis C Virus and Related Viruses, Kyoto,Japan, pp.

    Google Scholar 

  37. Murphy, D. G., Willems, B., Deschênes, M., Hilzenrat, N., Mousseau, R., and 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.

    Article  CAS  PubMed  Google Scholar 

  38. Kolykhalov, A. A., Feinstone, S. M., and Rice, C. M. (1996) Identification of a highly conserved sequence element at the 3′ terminus of hepatitis C virus genome RNA. J. Virol. 70, 3363–3371.

    CAS  PubMed  Google Scholar 

  39. Bukh, J., Purcell, R. H., and Miller, R. H. (1994) Sequence analysis of the core gene of 14 hepatitis C virus genotypes. Proc. Natl. Acad. Sci. USA 91, 8239–8243.

    Article  CAS  PubMed  Google Scholar 

  40. Enomoto, N., Takada, A., Nakao, T., and Date, T. (1990) There are two major types of hepatitis C virus in Japan. Biochem. Biophys. Res. Comm. 170, 1021–1025.

    Article  CAS  PubMed  Google Scholar 

  41. Korber, B., Foley, B., Kuiken, C., Pillai, S., and Sodroski, J. (1998) Numbering positions in HIV relative to HXB2CG, in Human Retroviruses and AIDS (Korber. B. K., Foley, C. L., Hahn, B., McCutchan, F., Mellors, J. W., and Sodroski, J., eds.), Los Alamos National Laboratory, Los Alamos, pp. 171–181.

    Google Scholar 

  42. Stuyver, L. J., Locarnini, S. A., Lok, A., Richman, D. D., Carman, W. F., Dienstag, J. L.,et al. Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region. Hepatology 33, 751–757.

    Google Scholar 

  43. Yanagi, M., Purcell, R. H., Emerson, S. U., and Bukh, J. (1997) Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. Proc. Natl. Acad. Sci. USA 94, 8738–8743.

    Article  CAS  PubMed  Google Scholar 

  44. Okamoto, H., Kojima, M., Okada, S., Yoshizawa, H., Iizuka, H., Tanaka, T., et al. (1992) Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability. Virology 190, 894–899.

    Article  CAS  PubMed  Google Scholar 

  45. Lucas, A. H., Moulton, K. D., and Reason, D. C. (1998) Role of kappa II-A2 light chain CDR-3 junctional residues in human antibody binding to the Haemophilus influenzae type b polysaccharide. J. Immunol. 161, 3776–3780.

    CAS  PubMed  Google Scholar 

  46. Kuiken, C., Mizokami, M., Deleage, G., Yusim, K., Penin, F., Tadasu, S.-I., et al. (2006) Hepatitis C databases, principles and utility to researchers. Hepatology 43, 1157–1165.

    Article  CAS  PubMed  Google Scholar 

  47. Yusim, K., Richardson, R., Tao, N., Dalwani, A., Agrawal, A., Szinger, J., et al. (2005) Los Alamos hepatitis C immunology database. Appl. Bioinformat. 4, 217–225.

    Article  CAS  Google Scholar 

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Acknowledgments

For their contributions, we thank Jens Bukh, Christophe Combet, Gilbert Deléage, Nobuyuki Enomoto, Stephen Feinstone, Phillippe Halfon, Geneviève Inchauspé, Geert Maertens, Masashi Mizokami, Donald G. Murphy, Hiroaki Okamoto, Jean-Michel Pawlotsky, François Penin, Erwin Sablon, Tadasu Shin-I, Lieven J. Stuyver, Heinz-Jürgen Thiel, Sergei Viazov, Amy J. Weiner, and Anders Widell.

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Authors and Affiliations

  1. Los Alamos National Laboratory, Los Alamos, NM, USA

    Carla Kuiken

  2. Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, UK

    Peter Simmonds

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  1. Carla Kuiken
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  2. Peter Simmonds
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  1. Florida State University, Tallahassee, FL, USA

    Hengli Tang

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Kuiken, C., Simmonds, P. (2009). Nomenclature and Numbering of the Hepatitis C Virus. In: Tang, H. (eds) Hepatitis C. Methods in Molecular Biology™, vol 510. Humana Press. https://doi.org/10.1007/978-1-59745-394-3_4

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  • DOI: https://doi.org/10.1007/978-1-59745-394-3_4

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-970-3

  • Online ISBN: 978-1-59745-394-3

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