1887

Abstract

Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A–I), and a putative 10th genotype (J), characterized thus far. Given the broadening interest in HBV sequencing, there is an increasing requirement for a consistent, unified approach to HBV genotype and subgenotype classification. We set out to generate an updated resource of reference sequences using the diversity of all genomic-length HBV sequences available in public databases. We collated and aligned genomic-length HBV sequences from public databases and used maximum-likelihood phylogenetic analysis to identify genotype clusters. Within each genotype, we examined the phylogenetic support for currently defined subgenotypes, as well as identifying well-supported clades and deriving reference sequences for them. Based on the phylogenies generated, we present a comprehensive set of HBV reference sequences at the genotype and subgenotype level. All of the generated data, including the alignments, phylogenies and chosen reference sequences, are available online (https://doi.org/10.6084/m9.figshare.8851946) as a simple open-access resource.

Funding
This study was supported by the:
  • Philippa C Matthews , Wellcome Trust , (Award 110110)
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001387
2020-03-05
2020-06-02
Loading full text...

Full text loading...

/deliver/fulltext/jgv/101/3/271.html?itemId=/content/journal/jgv/10.1099/jgv.0.001387&mimeType=html&fmt=ahah

References

  1. Locarnini S, Zoulim F. Molecular genetics of HBV infection. Antivir Ther 2010; 15:3–14 [CrossRef]
    [Google Scholar]
  2. McNaughton AL, D’Arienzo V, Ansari MA, Lumley SF, Littlejohn M et al. Insights from deep sequencing of the HBV genome—unique, tiny, and misunderstood. Gastroenterology 2019; 156:384–399 [CrossRef]
    [Google Scholar]
  3. Kramvis A. Genotypes and genetic variability of hepatitis B virus. Intervirology 2014; 57:141–150 [CrossRef]
    [Google Scholar]
  4. Torres-Cornejo A, Lauer GM. Hurdles to the development of effective HBV immunotherapies and HCV vaccines. Pathogens and Immunity 2017; 2:102 [CrossRef]
    [Google Scholar]
  5. Pawlotsky J-M, Negro F, Aghemo A, Berenguer M, Dalgard O et al. EASL recommendations on treatment of hepatitis C 2018. J Hepatol 2018; 69:461–511 [CrossRef]
    [Google Scholar]
  6. European Association for the Study of the Liver. Electronic address: [email protected] European Association for the Study of the Liver EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67:370–398 [CrossRef]
    [Google Scholar]
  7. Lin C-L, Kao J-H. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol 2011; 26:123–130 [CrossRef]
    [Google Scholar]
  8. Rajoriya N, Combet C, Zoulim F, Janssen HLA. How viral genetic variants and genotypes influence disease and treatment outcome of chronic hepatitis B. time for an individualised approach?. J Hepatol 2017; 67:1281–1297 [CrossRef]
    [Google Scholar]
  9. Pourkarim MR, Amini-Bavil-Olyaee S, Lemey P, Maes P, Van Ranst M. Are hepatitis B virus "subgenotypes" defined accurately?. J Clin Virol 2010; 47:356–360 [CrossRef]
    [Google Scholar]
  10. Jia L, Hu F, Li H, Li L, Tang X et al. Characterization of small genomic regions of the hepatitis B virus should be performed with more caution. Virol J 2018; 15:24–26 [CrossRef]
    [Google Scholar]
  11. Shi W, Zhang Z, Ling C, Zheng W, Zhu C et al. Hepatitis B virus subgenotyping: history, effects of recombination, misclassifications, and corrections. Infection, Genetics and Evolution 2013; 16:355–361 [CrossRef]
    [Google Scholar]
  12. Schaefer S, Magnius L, Norder H. Under construction: classification of hepatitis B virus genotypes and subgenotypes. Intervirology 2009; 52:323–325 [CrossRef]
    [Google Scholar]
  13. Ahn SH, Yuen L, Revill P. Clarification required for the definition of hepatitis B virus subgenotypes C1 and C2. Intervirology 2009; 52:321–322 [CrossRef]
    [Google Scholar]
  14. Hayer J, Jadeau F, Deléage G, Kay A, Zoulim F et al. HBVdb: a knowledge database for hepatitis B virus. Nucleic Acids Res 2013; 41:D566–D570 [CrossRef]
    [Google Scholar]
  15. Panjaworayan N, Roessner SK, Firth AE, Brown CM. HBVRegDB: annotation, comparison, detection and visualization of regulatory elements in hepatitis B virus sequences. Virol J 2007; 4:136–10 [CrossRef]
    [Google Scholar]
  16. Bell TG, Yousif M, Kramvis A. Bioinformatic curation and alignment of genotyped hepatitis B virus (HBV) sequence data from the GenBank public database. Springerplus 2016; 5:1896 [CrossRef]
    [Google Scholar]
  17. Kramvis A, Arakawa K, Yu MC, Nogueira R, Stram DO et al. Relationship of serological subtype, basic core promoter and precore mutations to genotypes/subgenotypes of hepatitis B virus. J Med Virol 2008; 80:27–46 [CrossRef]
    [Google Scholar]
  18. Kim H, Lee S-A, Kim D-W, Lee S-H, Kim B-J. Naturally occurring mutations in large surface genes related to occult infection of hepatitis B virus genotype C. PLoS One 2013; 8:e54486 [CrossRef]
    [Google Scholar]
  19. Skelton M, Kew MC, Kramvis A. Distinct mutant hepatitis B virus genomes, with alterations in all four open reading frames, in a single South African hepatocellular carcinoma patient. Virus Res 2012; 163:59–65 [CrossRef]
    [Google Scholar]
  20. Valenzuela P, Quiroga M, Zaldivar J, Gray P, Rutter WJ. The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes. Animal Virus Genetics 198057–70
    [Google Scholar]
  21. Mühlemann B, Jones TC, Damgaard PdeB, Allentoft ME, Shevnina I et al. Ancient hepatitis B viruses from the bronze age to the medieval period. Nature 2018; 557:418–423 [CrossRef]
    [Google Scholar]
  22. Patterson Ross Z, Klunk J, Fornaciari G, Giuffra V, Duchêne S et al. The paradox of HBV evolution as revealed from a 16th century mummy. PLoS Pathog 2018; 14:e1006750 [CrossRef]
    [Google Scholar]
  23. Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 1979; 281:646–650 [CrossRef]
    [Google Scholar]
  24. Katoh K, Rozewicki J, Yamada KD. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform 2019; 20:1160–1166 [CrossRef]
    [Google Scholar]
  25. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014; 30:1312–1313 [CrossRef]
    [Google Scholar]
  26. Hatakeyama T, Noguchi C, Hiraga N, Mori N, Tsuge M et al. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine. Hepatology 2007; 45:1179–1186 [CrossRef]
    [Google Scholar]
  27. Mulyanto M, Depamede SN, Surayah K, Tjahyono AAH et al. Identification and characterization of novel hepatitis B virus subgenotype C10 in NusA Tenggara, Indonesia. Arch Virol 2010; 155:705–715 [CrossRef]
    [Google Scholar]
  28. Mulyanto S, Depamede SN, Wahyono A, Jirintai N, Nagashima S et al. Analysis of the full-length genomes of novel hepatitis B virus subgenotypes C11 and C12 in Papua, Indonesia. J Med Virol 2011; 83:54–64 [CrossRef]
    [Google Scholar]
  29. Cavinta L, Sun J, May A, Yin J, von Meltzer M et al. A new isolate of hepatitis B virus from the Philippines possibly representing a new subgenotype C6. J Med Virol 2009; 81:983–987 [CrossRef]
    [Google Scholar]
  30. Mulyanto N, Pancawardani P, Depamede SN, Wahyono A, Jirintai S et al. Identification of four novel subgenotypes (C13-C16) and two inter-genotypic recombinants (C12/G and C13/B3) of hepatitis B virus in Papua Province, Indonesia. Virus Res 2012; 163:129–140 [CrossRef]
    [Google Scholar]
  31. Paraskevis D, Magiorkinis G, Magiorkinis E, Ho SYW, Belshaw R et al. Dating the origin and dispersal of hepatitis B virus infection in humans and primates. Hepatology 2013; 57:908–916 [CrossRef]
    [Google Scholar]
  32. Zehender G, Ebranati E, Gabanelli E, Shkjezi R, Lai A et al. Spatial and temporal dynamics of hepatitis B virus D genotype in Europe and the mediterranean basin. PLoS One 2012; 7:e37198–8 [CrossRef]
    [Google Scholar]
  33. Paraskevis D, Angelis K, Magiorkinis G, Kostaki E, Ho SYW et al. 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 [CrossRef]
    [Google Scholar]
  34. Livingston SE, Simonetti JP, McMahon BJ, Bulkow LR, Hurlburt KJ et al. Hepatitis B virus genotypes in Alaska native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis 2007; 195:5–11 [CrossRef]
    [Google Scholar]
  35. Marciano S, Galdame OA, Gadano AC. HBV genotype F: natural history and treatment. Antivir Ther 2013; 18:485–488 [CrossRef]
    [Google Scholar]
  36. van der Kuyl AC, Zorgdrager F, Hogema B, Bakker M, Jurriaans S et al. High prevalence of hepatitis B virus dual infection with genotypes A and G in HIV-1 infected men in Amsterdam, the Netherlands, during 2000-2011. BMC Infect Dis 2013; 13:540 [CrossRef]
    [Google Scholar]
  37. Pourkarim MR, Lemey P, Amini-Bavil-Olyaee S, Maes P, Van Ranst M. Novel hepatitis B virus subgenotype A6 in African-Belgian patients. J Clin Virol 2010; 47:93–96 [CrossRef]
    [Google Scholar]
  38. Mühlemann B, Jones TC, Damgaard PdeB, Allentoft ME, Shevnina I et al. Ancient hepatitis B viruses from the bronze age to the medieval period. Nature 2018; 557:418–423 [CrossRef]
    [Google Scholar]
  39. Hraber PT, Fischer W, Bruno WJ, Leitner T, Kuiken C. Comparative analysis of hepatitis C virus phylogenies from coding and non-coding regions: the 5’ untranslated region (UTR) fails to classify subtypes. Virol J 2006; 3:103 [CrossRef]
    [Google Scholar]
  40. Ogden TH, Rosenberg MS. Multiple sequence alignment accuracy and phylogenetic inference. Syst Biol 2006; 55:314–328 [CrossRef]
    [Google Scholar]
  41. Yin Y, He K, Wu B, Xu M, Du L et al. A systematic genotype and subgenotype re-ranking of hepatitis B virus under a novel classification standard. Heliyon 2019; 5:e02556 [CrossRef]
    [Google Scholar]
  42. Niebel M, Singer JB, Nickbakhsh S, Gifford RJ, Thomson EC. Hepatitis C and the absence of genomic data in low-income countries: a barrier on the road to elimination?. Lancet Gastroenterol Hepatol 2017; 2:700–701 [CrossRef]
    [Google Scholar]
  43. Cai Q, Zhu H, Zhang Y, Li X, Zhang Z. Hepatitis B virus genotype A: design of reference sequences for sub-genotypes. Virus Genes 2016; 52:325–333 [CrossRef]
    [Google Scholar]
  44. Zhu HL, Wang CT, Xia JB, Li X, Zhang ZH. Establishment of reference sequences of hepatitis B virus genotype C subgenotypes. Genet Mol Res 2015; 14:16521–16534 [CrossRef]
    [Google Scholar]
  45. Castelhano N, Araujo NM, Arenas M. Heterogeneous recombination among hepatitis B virus genotypes. Infect Genet Evol 2017; 54:486–490 [CrossRef]
    [Google Scholar]
  46. Simmonds P, Midgley S. Recombination in the genesis and evolution of hepatitis B virus genotypes. J Virol 2005; 79:15467–15476 [CrossRef]
    [Google Scholar]
  47. Tatematsu K, Tanaka Y, Kurbanov F, Sugauchi F, Mano S et al. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol 2009; 83:10538–10547 [CrossRef]
    [Google Scholar]
  48. Shi W, Zhu C, Zheng W, Zheng W, Ling C et al. Subgenotyping of genotype C hepatitis B virus: correcting Misclassifications and identifying a novel subgenotype. PLoS One 2012; 7:e47271 [CrossRef]
    [Google Scholar]
  49. Del Campo JA, Parra-Sánchez M, Figueruela B, García-Rey S, Quer J et al. Hepatitis C virus deep sequencing for sub-genotype identification in mixed infections: a real-life experience. Int J Infect Dis 2018; 67:114–117 [CrossRef]
    [Google Scholar]
  50. Fokam J, Bellocchi MC, Armenia D, Nanfack AJ, Carioti L et al. Next-Generation sequencing provides an added value in determining drug resistance and viral tropism in cameroonian HIV-1 vertically infected children. Medicine 2018; 97:e0176 [CrossRef]
    [Google Scholar]
  51. Davis C, Mgomella GS, da Silva Filipe A, Frost EH, Giroux G et al. Highly diverse hepatitis C strains detected in sub-Saharan Africa have unknown susceptibility to direct-acting antiviral treatments. Hepatology 2019; 69:1426–1441 [CrossRef]
    [Google Scholar]
  52. Borgia SM, Hedskog C, Parhy B, Hyland RH, Stamm LM et al. Identification of a novel hepatitis C virus genotype from Punjab, India: expanding classification of hepatitis C virus into 8 genotypes. J Infect Dis 2018; 218:1722–1729 [CrossRef]
    [Google Scholar]
  53. Shi W, Zhu C, Zheng W, Carr MJ, Higgins DG et al. Subgenotype reclassification of genotype B hepatitis B virus. BMC Gastroenterol 2012; 12:2–7 [CrossRef]
    [Google Scholar]
  54. Yousif M, Kramvis A. Genotype D of hepatitis B virus and its subgenotypes: an update. Hepatol Res 2013; 43:355–364 [CrossRef]
    [Google Scholar]
  55. Ochwoto M, Kimotho JH, Oyugi J, Okoth F, Kioko H et al. Hepatitis B infection is highly prevalent among patients presenting with jaundice in Kenya. BMC Infect Dis 2016; 16:101
    [Google Scholar]
  56. Andernach IE, Nolte C, Pape JW, Muller CP. Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa. Emerg Infect Dis 2009; 15:1222–1228
    [Google Scholar]
  57. Tallo T, Norder H, Tefanova V, Krispin T, Priimägi L et al. Hepatitis B virus genotype D strains from Estonia share sequence similarity with strains from Siberia and may specify ayw4. J Med Virol 2004; 74:221–227 [CrossRef]
    [Google Scholar]
  58. Makuwa M, Souquière S, Telfer P, Apetrei C, Vray M et al. Identification of hepatitis B virus subgenotype A3 in rural Gabon. J Med Virol 2006; 78:1175–1184
    [Google Scholar]
  59. Loureiro CL, Aguilar JC, Aguiar J, Muzio V, Pentón E et al. Hbv genotypic variability in Cuba. PLoS One 2015; 10:e0118959
    [Google Scholar]
  60. Andernach IE, Nolte C, Pape JW, Muller CP. Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa. Emerg Infect Dis 2009; 15:1222–1228
    [Google Scholar]
  61. Horikita M, Itoh S, Yamamoto K, Shibayama T, Tsuda F et al. Differences in the entire nucleotide sequence between hepatitis B virus genomes from carriers positive for antibody to hepatitis B e antigen with and without active disease. J Med Virol 1994; 44:96–103
    [Google Scholar]
  62. Tangkijvanich P, Sa-Nguanmoo P, Avihingsanon A, Ruxrungtham K, Poovorawan K et al. Characterization of hepatitis B virus mutations in untreated patients co-infected with HIV and HBV based on complete genome sequencing. J Med Virol 2013; 85:16–25
    [Google Scholar]
  63. Wang H-Y, Chien M-H, Huang H-P, Chang H-C, Wu C-C et al. Distinct hepatitis B virus dynamics in the immunotolerant and early immunoclearance phases. J Virol 2010; 84:3454–3463 [CrossRef]
    [Google Scholar]
  64. Mulyanto M, Depamede SN, Surayah K, Tsuda F, Ichiyama K et al. A nationwide molecular epidemiological study on hepatitis B virus in Indonesia: identification of two novel subgenotypes, B8 and C7. Arch Virol 2009; 154:1047–1059 [CrossRef]
    [Google Scholar]
  65. Sugauchi F, Orito E, Ichida T, Kato H, Sakugawa H et al. Hepatitis B virus of genotype B with or without recombination with genotype C over the precore region plus the core gene. J Virol 2002; 76:5985–5992
    [Google Scholar]
  66. Sakamoto T, Tanaka Y, Simonetti J, Osiowy C, Borresen ML et al. Classification of hepatitis B virus genotype B into 2 major types based on characterization of a novel subgenotype in Arctic Indigenous populations. J Infect Dis 2007; 196:1487–1492
    [Google Scholar]
  67. Chan HLY, Tsui SKW, Tse C-H, Ng EYT, Au TCC et al. Epidemiological and virological characteristics of 2 subgroups of hepatitis B virus genotype C. J Infect Dis 2005; 191:2022–2032 [CrossRef]
    [Google Scholar]
  68. Chen X, Gao J, Ji Z, Zhang W, Zhang L et al. A description of the hepatitis B virus genomic background in a high-prevalence area in China. Virol J 2014; 11:101
    [Google Scholar]
  69. Xu Z, Liu Y, Xu T, Chen L, Si L et al. Acute hepatitis B infection associated with drug-resistant hepatitis B virus. J Clin Virol 2010; 48:270–274
    [Google Scholar]
  70. Mulyanto M, Depamede SN, Surayah K, Tsuda F, Ichiyama K et al. A nationwide molecular epidemiological study on hepatitis B virus in Indonesia: identification of two novel subgenotypes, B8 and C7. Arch Virol 2009; 154:1047–1059 [CrossRef]
    [Google Scholar]
  71. Littlejohn M, Davies J, Yuen L, Edwards R, Sozzi T et al. Molecular virology of hepatitis B virus, sub-genotype C4 in northern Australian Indigenous populations. J Med Virol 2014; 86:695–706
    [Google Scholar]
  72. Li Z, Xie Z, Ni H, Zhang Q, Lu W et al. Mother-To-Child transmission of hepatitis B virus: evolution of hepatocellular carcinoma-related viral mutations in the post-immunization era. J Clin Virol 2014; 61:47–54
    [Google Scholar]
  73. Avazova D, Kurbanov F, Tanaka Y, Sugiyama M, Radchenko I et al. Hepatitis B virus transmission pattern and vaccination efficiency in Uzbekistan. J Med Virol 2008; 80:217–224
    [Google Scholar]
  74. Datta S, Ghosh A, Dasgupta D, Ghosh A, Roychoudhury S et al. Novel point and combo-mutations in the genome of hepatitis B virus-genotype D: characterization and impact on liver disease progression to hepatocellular carcinoma. PLoS One 2014; 9:e110012
    [Google Scholar]
  75. Munshi SU, Tran TTT, Vo TNT, Tabassum S, Sultana N et al. Molecular characterization of hepatitis B virus in Bangladesh reveals a highly recombinant population. PLoS One 2017; 12:e0188944
    [Google Scholar]
  76. Ghosh S, Banerjee P, RoyChoudhury A, Sarkar S, Ghosh A et al. Unique hepatitis B virus subgenotype in a primitive tribal community in eastern India. J Clin Microbiol 2010; 48:4063–4071
    [Google Scholar]
  77. Meldal BHM, Moula NM, Barnes IHA, Boukef K, Allain J-P. A novel hepatitis B virus subgenotype, D7, in Tunisian blood donors. J Gen Virol 2009; 90:1622–1628
    [Google Scholar]
  78. Garmiri P, Loua A, Haba N, Candotti D, Allain J-P. Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in guinea, West Africa. J Gen Virol 2009; 90:2442–2451
    [Google Scholar]
  79. Venegas M, Alvarado-Mora MV, Villanueva RA, Rebello Pinho JR, Carrilho FJ et al. Phylogenetic analysis of hepatitis B virus genotype F complete genome sequences from Chilean patients with chronic infection. J Med Virol 2011; 83:1530–1536
    [Google Scholar]
  80. Devesa M, Loureiro CL, Rivas Y, Monsalve F, Cardona N et al. Subgenotype diversity of hepatitis B virus American genotype F in Amerindians from Venezuela and the general population of Colombia. J Med Virol 2008; 80:20–26
    [Google Scholar]
  81. Blanco RY, Loureiro CL, Villalba JA, Sulbarán YF, Maes M et al. Decreasing prevalence of hepatitis B and absence of hepatitis C virus infection in the Warao Indigenous population of Venezuela. PLoS One 2018; 13:e0197662
    [Google Scholar]
  82. González López Ledesma MM, Mojsiejczuk LN, Rodrigo B, Sevic I, Mammana L et al. Hepatitis B virus genotype distribution and genotype-specific BCP/preCore substitutions in acute and chronic infections in Argentina. PLoS One 2015; 10:e0121436
    [Google Scholar]
  83. Kato H, Orito E, Sugauchi F, Ueda R, Gish RG et al. Determination of hepatitis B virus genotype G by polymerase chain reaction with hemi-nested primers. J Virol Methods 2001; 98:153–159
    [Google Scholar]
  84. Flichman D, Galdame O, Livellara B, Viaut M, Gadano A et al. Full-Length genome characterization of hepatitis B virus genotype H strain isolated from serum samples collected from two chronically infected patients in Argentina. J Clin Microbiol 2009; 47:4191–4193 [CrossRef]
    [Google Scholar]
  85. Nguyen CH, Ishizaki A, Chung PTT, Hoang HT, Nguyen TV et al. Prevalence of HBV infection among different HIV-risk groups in HAI Phong, Vietnam. J Med Virol 2011; 83:399–404
    [Google Scholar]
  86. Olinger CM, Jutavijittum P, Hübschen JM, Yousukh A, Samountry B et al. Possible new hepatitis B virus genotype, Southeast Asia. Emerg Infect Dis 2008; 14:1777–1780
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001387
Loading
/content/journal/jgv/10.1099/jgv.0.001387
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error