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Genetic variability of hepatitis B virus in Uruguay: D/F, A/F genotype recombinants

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Abstract

Hepatitis B virus (HBV) infection is a serious global health problem. Approximately 2 billion people worldwide have been infected, and approximately 350 million individuals currently suffer from HBV-induced chronic liver infection, which causes 600,000 deaths annually from chronic hepatitis, cirrhosis and hepatocellular carcinoma. HBV is classified in eight genotypes (A-H), and two more have been proposed (I-J). In this paper, complete genome sequences of nine Uruguayan HBV are reported. Five samples belong to genotype F1b and one to genotype A2. Three HBV recombinants were detected: A1/F1b, A2/F1b and D3/F1b. The following mutations were detected: a G1896A substitution, a 33-nucleotide deletion from position 2896 to 2928 in the Pre-S1 region involving Pre-S1 residues 3-13, a 33-nt deletion in the Pre-S1 region involving nt 2913-2945 and Pre-S1 residues 9-19. More F genotypes strains than expected were detected in this study, supporting the hypothesis that there are more people of indigenous origin than declared in our population. Also, one third of the samples analyzed were recombinants. This cannot be explained by the low HBV prevalence in Uruguay, but a high HBV infection rate in drug addicts and dialysis patients could act in favor of multiple-genotype HBV infections that could lead to recombination.

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References

  1. Hepatitis B World Health Organization Fact Sheet No 204. http://www.who.int/mediacentre/factsheets/fs204/en/index.html. Accessed 27 Nov 2014

  2. Lopez L, Lopez P, Arago A, Rodríguez I, Lopez J, Lima E, Insagaray J, Bentancor N (2005) Risk factors for hepatitis B and C in multi-transfused patients in Uruguay. J Clin Virol 34(2):S69–S74

    Article  PubMed  Google Scholar 

  3. Osimani ML, Vázquez R, Chiparelli H, Guchin M, Latorre L, Garibotto G, Gherardi A, Vidal J (2005) Seroprevalencia para los virus de la inmunodeficiencia humana, hepatitis B y C en usuarios de drogas inyectables. Rev Med Urug 21:207–214

    Google Scholar 

  4. Kramvis A (2014) Genotypes and genetic variability of hepatitis B virus. Intervirology 57(3–4):141–150. doi:10.1159/000360947

    Article  PubMed  Google Scholar 

  5. Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F (2014) Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol 20(23):7152–7168. doi:10.3748/wjg.v20.i23.7152

    Article  PubMed Central  PubMed  Google Scholar 

  6. Magnius LO, Norder H (1995) Subtypes, genotypes and molecular epidemiology of the hepatitis virus as reflected by sequence variability of the S gene. Intervirology 38:24–34

    CAS  PubMed  Google Scholar 

  7. Norder H, Couroucé AM, Magnius LO (1994) Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes. Virology 198:489–503

    Article  CAS  PubMed  Google Scholar 

  8. Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi R et al (2000) A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol 81:67–74

    Article  CAS  PubMed  Google Scholar 

  9. Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO (2002) Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America. J Gen Virol 83:2059–2073

    Article  CAS  PubMed  Google Scholar 

  10. Olinger CM, Lazouskaya NV, Eremin VF, Muller CP (2008) Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences. Clin Microbiol Infect 14:575–581

    Article  CAS  PubMed  Google Scholar 

  11. Tatematsu K, Tanaka Y, Kurbanov F, Sugauchi F, Mano S, Maeshiro T, Nakayoshi T, Wakuta M, Miyakawa Y, Mizokami M (2009) 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 83:10538–10547

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Shi W, Zhang Z, Ling C, Zheng W, Zhu C, Carr MJ, Higgins DG (2013) Hepatitis B virus subgenotyping: history, effects of recombination, misclassifications, and corrections. Infect Genet Evol 16:355–361

    Article  CAS  PubMed  Google Scholar 

  13. Zhang Q, Cao G (2011) Genotypes, mutations, and viral load of hepatitis B virus and the risk of hepatocellular carcinoma. Hepat Mon 11:86–91

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Sugauchi F, Kumada H, Acharya SA, Shrestha SM, Gamutan MTA, Khan M et al (2004) Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A. J Gen Virol 85:811–820

    Article  CAS  PubMed  Google Scholar 

  15. Kurbanov F, Tanaka Y, Fujiwara K, Sugauchi F, Mbanya D, Zekeng L, Ndembi N, Ngansop C, Kaptue L, Miura T, Ido E, Hayami M, Ichimura H, Mizokami M (2005) A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination between genotypes A and E in Cameroon. J Gen Virol 86:2047–2056

    Article  CAS  PubMed  Google Scholar 

  16. Hannoun C, Söderström A, Norkrans G, Lindh M (2005) Phylogeny of African complete genomes reveals a West African genotype A subtype of hepatitis B virus and relatedness between Somali and Asian A1 sequences. J Gen Virol 86(Pt 8):2163–2167

    Article  CAS  PubMed  Google Scholar 

  17. Olinger CM, Venard V, Njayou M, Oyefolu AO, Maiga I, Kemp AJ, Omilabu SA, le Faou A, Muller CP (2006) Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol 87:1163–1173

    Article  CAS  PubMed  Google Scholar 

  18. Pourkarim MR, Lemey P, Amini-Bavil-Olyaee S, Maes P, Van Ranst M (2010) Novel hepatitis B virus subgenotype A6 in African-Belgian patients. J Clin Virol 47(1):93–96. doi:10.1016/j.jcv.2009.09.032

    Article  CAS  PubMed  Google Scholar 

  19. Hübschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM, Charpentier E, Muller CP (2011) Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect 17(1):88–94

    Article  PubMed  Google Scholar 

  20. Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, Robertson BH, Locarnini S, Magnius LO (2004) Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 47:289–309

    Article  PubMed  Google Scholar 

  21. Huy TTT, Ushijima H, Quang VX, Win KM, Luengrojanakul P, Kikuchi K, Sata T, Abe K (2004) Genotype C of hepatitis B virus can be classified into at least two subgroups. J Gen Virol 85:283–292

    Article  CAS  PubMed  Google Scholar 

  22. Kramvis A, Kew MC, François G (2005) Hepatitis B virus genotypes. Vaccine 23:2409–2423

    Article  CAS  PubMed  Google Scholar 

  23. Yousif M, Kramvis A (2013) Genotype D of hepatitis B virus and its subgenotypes: an update. Hepatol Res 43(4):355–364

    Article  CAS  PubMed  Google Scholar 

  24. Kidd-Ljunggren K, Myhre E, Blackberg J (2004) Clinical and serological variation between patients infected with different hepatitis virus genotypes. J Clin Microbiol 42:5837–5841

    Article  PubMed Central  PubMed  Google Scholar 

  25. Arauz-Ruiz P, Norder H, Visoná KA, Magnius LO (1997) Molecular epidemiology of hepatitis B virus in Central America reflected in the genetic variability of the small S gene. J Infect Dis 176(4):851–858

    Article  CAS  PubMed  Google Scholar 

  26. Huy TTT, Ushijima H, Sata T, Abe K (2006) Genomic characterization of HBV genotype F in Bolivia: genotype F subgenotypes correlate with geographic distribution and T1858 variant. Arch Virol 151:589–597

    Article  CAS  PubMed  Google Scholar 

  27. Campos RH, Mbayed VA, Piñeiro y Leone FG (2005) Molecular epidemiology of hepatitis B virus in Latin America. J Clin Virol 34:S8–S13

    Article  CAS  PubMed  Google Scholar 

  28. Devesa M, Loureiro C, Rivas Y et al (2008) Subgenotype diversity of hepatitis B virus American genotype F in Amerindians from Venezuela and the general population in Colombia. J Med Virol 80:20–26

    Article  CAS  PubMed  Google Scholar 

  29. Livingston SE, Simonetti JP, McMahon BJ, Bulkow LR, Hurlburt KJ, Homan CE, Snowball MM, Cagle HH, Williams JL, Chulanov VP (2007) Hepatitis B virus genotypes in Alaska native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis 195(1):5–11

    Article  CAS  PubMed  Google Scholar 

  30. Piñeiro y Leone FG, Mbayed VA, Campos RH (2003) Evolutionary history of hepatitis B virus genotype F: an in-depth analysis of Argentine isolates. Virus Genes 27:103–110

    Article  PubMed  Google Scholar 

  31. Araujo NM, Mello FCA, Yoshida CFT, Niel C, Gomes SA (2004) High prevalence of subgroup A (genotype A) among Brazilian isolates of hepatitis B virus. Arch Virol 149:1383–1395

    Article  CAS  PubMed  Google Scholar 

  32. Sitnik R, Pinho JR, Bertolini DA, Bernardini AP, Da Silva LC, Carrilho FJ (2004) Hepatitis B virus genotypes and precore and core mutants in Brazilian patients. J Clin Microbiol 42:2455–2460

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Martinez AA, Zaldivar Y, Ch Hong Ch, Alvarado-Mora M, Smith R, Ortiz AY, Rebello JR, Cristina J, Pascale JM (2013) Molecular characterization of hepatitis B virus in the resident Chinese population in Panama City. Mem Inst Oswaldo Cruz 108:541–547

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Franca PH, Gonzalez JE, Munne MS, Brandao LH, GouveaVS Sablon E et al (2004) Strong association between genotype F and hepatitis B virus (HVB) e antigen-negative variants among HBV-infected Argentinean blood donors. J Clin Microbiol 42:5015–5021

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Rezende REF, Fonseca BAL, Ramalho LNZ, Zucoloto S, Pinho JRR, Bertolini DA et al (2005) The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B. J Clin Virol 32:53–59

    Article  CAS  PubMed  Google Scholar 

  36. Rebaglaitti P, Colina R, Garcia L, Uriarte R, Mogdasy C, Cristina J (2000) Hepatitis B virus core promoter genetic variability and the role of mutations in disease outcome. Virus Res 5:41–48

    Google Scholar 

  37. Devesa M, Pujol FH (2007) Hepatitis B virus genetic diversity in Latin America. Virus Res 127:177–184

    Article  CAS  PubMed  Google Scholar 

  38. Mello F, Araujo O, Lago B, Motta-Castro A, Moraes M, Gomes S, Bello G, Araujo N (2013) Phylogeography and evolutionary history of hepatitis B virus genotype F in Brazil. Virol J 10:236–243

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Mello FC, Souto FJ, Nabuco LC, Villela-Nogueira CA, Coelho HS, Franz HC, Saraiva JC, Virgolino HA, Motta-Castro AR, Melo MM, Martins RM, Gomes SA (2007) Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates. BMC Microbiol 7:103

    Article  PubMed Central  PubMed  Google Scholar 

  40. Alvarado-Mora MV, Pinho JR (2013) Distribution of HBV genotypes in Latin America. Antivir Ther 18(3 Pt B):459–465. doi:10.3851/IMP2599

    Article  PubMed  Google Scholar 

  41. Barbini L, Tadey L, Fernandez S, Bouzas B, Campos R (2012) Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients. Virol J 9:131. doi:10.1186/1743-422X-9-131

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Venegas M, Alvarado M, Villanueva R, Rebello J, Carrilho F, Locarnini S, Yuen L, Brahm J (2011) Phylogenetic analysis of hepatitis b virus genotype F complete genome sequences from Chilean patients with chronic infection. J Med Virol 83:1530–1536

    Article  CAS  PubMed  Google Scholar 

  43. Gallego F, Pisano MB, Torres C, Caeiro L, Martínez Wassaf M, Balangero M, Campos R (2014) Molecular epidemiology of hepatitis B virus in Córdoba, Argentina. J Clin Virol 61(2):204–210. doi:10.1016/j.jcv.2014.06.030

    Article  PubMed  Google Scholar 

  44. Santos A, Alvarado M, Botelho L, Vieira D, Rebello J, Carrilho F, Honda E, Salcedo J (2010) Characterization of hepatitis B virus (HBV) genotypes in patients from Rondônia, Brazil. Virol J 7:315–321

    Article  PubMed Central  PubMed  Google Scholar 

  45. Rios-Ocampo WA, Cortes-Mancera F, Olarte JC, Soto A, Navas MC (2014) Occult hepatitis B virus infection among blood donors in Colombia. Virol J 11:206. doi:10.1186/s12985-014-0206-z

    Article  PubMed Central  PubMed  Google Scholar 

  46. Martínez AA, Zaldivar YY, CSS-NAT Group, De Castillo Z, Ortiz AY, Mendoza Y, Cristina J, Pascale JM (2014) High diversity of hepatitis B virus genotypes in Panamanian blood donors: a molecular analysis of new variants. PLoS One 9(8):e103545. doi:10.1371/journal.pone.0103545 (eCollection 2014)

    Article  PubMed Central  PubMed  Google Scholar 

  47. Shi Y (2012) Correlation between hepatitis B virus genotypes and clinical outcomes. Jpn J Infect Dis 65:476–482

    Article  PubMed  Google Scholar 

  48. Echevarria JM, Avellon A (2006) Hepatitis B virus genetic diversity. J Med Virol 78:S36–S42

    Article  CAS  PubMed  Google Scholar 

  49. El Khouri ME, Dos Santos VA (2004) Hepatitis B: epidemiological, immunological and serological considerations emphasizing mutation. Rev Hosp Clín Fac Med Sao Paulo 59:216–224

    PubMed  Google Scholar 

  50. Yap SF, Wong PW, Chen YC, Rosmawati M (2002) The frequency of pre-core gene mutations in chronic hepatitis B infection: a study of Malaysian subjects. Southeast Asian J Trop Med Public Health 33:102–107

    CAS  PubMed  Google Scholar 

  51. Sievers F, Wilm A, Dineen DG, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins D (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7. Article number: 539. doi:10.1038/msb.2011.75

  52. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O (2010) New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 59(3):307–321

    Article  CAS  PubMed  Google Scholar 

  53. Anisimova M, Gascuel O (2006) Approximate likelihood ratio test for branch: a fast, accurate and powerful alternative. Syst Biol 55:539–552

    Article  PubMed  Google Scholar 

  54. Shimodaira H (2003) An approximately unbiased test of phylogenetic tree selection. Syst Biol 51:492–508

    Article  Google Scholar 

  55. Shimodaira H, Hasegawa M (2001) CONSEL: for assessing the confidence of phylogenetic tree selection. Bioinformatics 17:1246–1247

    Article  CAS  PubMed  Google Scholar 

  56. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23(21):2947–2948. doi:10.1093/bioinformatics/btm404

    Article  CAS  PubMed  Google Scholar 

  57. Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41:95–98

    CAS  Google Scholar 

  58. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Korber B, Myers G (1992) Signature pattern analysis: a method for assessing viral sequence relatedness. AIDS Res Hum Retrovir 8(9):1549–1560

    Article  CAS  PubMed  Google Scholar 

  60. Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73(1):152–160

    PubMed Central  CAS  PubMed  Google Scholar 

  61. Araujo NM, Vianna CO, Moraes MTB, Gomes S (2009) Expression of hepatitis B virus surface antigen (HBsAg) from genotypes A, D and F and influence of amino acid variations related or not to genotypes on HBsAg detection. Braz J Infect Dis 13(4):266–271

    Article  CAS  PubMed  Google Scholar 

  62. Barbini L, Elizalde M, Torres C, Campos R (2013) Molecular epidemiology and genetic diversity of hepatitis B virus in Mar del Plata city, Argentina. Infect Genet Evol 19:152–163

    Article  CAS  PubMed  Google Scholar 

  63. Gallego F, Pisano MB, Torres C, Caeiro L, Martinez Wassaf M, Balangero M, Campos R, Ré V (2014) Molecular epidemiology of hepatitis B virus in Córdoba, Argentina. J Clin Virol 61:204–210

    Article  PubMed  Google Scholar 

  64. Sans M (2009) Raza, adscripción étnica y genética en Uruguay. Runa XXX(2):163–174. FFyL-UBA-ISSN: 0325-1217

  65. Kay A, Zoulim F (2007) Hepatitis B virus genetic variability and evolution. Virus Res 127:164–176

    Article  CAS  PubMed  Google Scholar 

  66. Simmonds P, Midgley S (2005) Recombination in the genesis and evolution of hepatitis B virus genotypes. J Virol 79(24):15467–15476

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Alvarado M, Romano C, Gomes M, Gutierrez M, Carrilho F (2012) Phylogenetic analysis of complete genome sequences of hepatitis B virus from an Afro-Colombian community: presence of HBV F3/A1 recombinant strain. Virol J 9:244

    Article  Google Scholar 

  68. Araujo NM, Araujo OC, Silva EM, Villela-Nogueira CA, Nabuco LC, Parana R, Bessone F, Gomes SA, Trepo C, Kay A (2013) Identification of novel recombinants of hepatitis B virus genotypes F and G in human immunodeficiency virus-positive patients from Argentina and Brazil. J Gen Virol 94(Pt 1):150–158. doi:10.1099/vir.0.047324-0

    Article  CAS  PubMed  Google Scholar 

  69. Cento V, Mirabelli C, Dimonte S, Salpini R, Han Y, Trimoulet P, Bertoli A, Micheli V, Gubertini G, Cappiello G, Spanò A, Longo R, Bernassola M, Mazzotta F, De Sanctis GM, Zhang XX, Verheyen J, D’Arminio Monforte A, Ceccherini-Silberstein F, Perno CF, Svicher V (2013) Overlapping structure of hepatitis B virus (HBV) genome and immune selection pressure are critical forces modulating HBV evolution. J Gen Virol 94:143–149

    Article  CAS  PubMed  Google Scholar 

  70. Torres C, Fernández MD, Flichman DM, Campos RH, Mbayed VA (2013) Influence of overlapping genes on the evolution of human hepatitis B virus. Virology 441(1):40–48

    Article  CAS  PubMed  Google Scholar 

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Lopez, L., Flichman, D., Mojsiejczuk, L. et al. Genetic variability of hepatitis B virus in Uruguay: D/F, A/F genotype recombinants. Arch Virol 160, 2209–2217 (2015). https://doi.org/10.1007/s00705-015-2477-0

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