1887

Abstract

Yunnan is considered to be a geographical hotspot for the introduction, mutation and recombination of several viruses in China. However, there are limited data regarding the genotypic profiles of hepatitis B virus (HBV) in this region. In this study, we characterized 206 HBV strains isolated from chronic hepatitis B patients in Yunnan, China. Initial genotyping based on 1.5 kb sequences revealed that genotype C was the most prevalent at 52.4 % (108/206), followed by genotype B at 30.6 % (63/206) and unclassified genotypes at 17.0 % (35/206). To characterize the 35 unclassified strains, 32 complete HBV genomes were amplified and analysed; 17 isolates were classified within a known subgenotype, 8 were classified as B/C recombinants, 1 was classified as a B/I recombinant and 6 constituted a potentially novel C subgenotype that we designated as C17, based on the characteristics of a monophyletic cluster, >4 % genetic distances, no significant evidence of recombination and no epidemiological link among individuals. Thus, multiple subgenotypes – namely B1, B2, B4, C1, C2, C3, C4, C8 and C17 – and two distinct intergenotypic recombinants exist in Yunnan, China, highlighting the complex and diverse distribution pattern of HBV genotypic profiles.

Funding
This study was supported by the:
  • National Natural Science Foundation of China (Award 81601767)
  • Key Project of Yunnan Education Department (Award 2015Z073)
  • New Product Development Projects of Yunnan Province (Award 2016BC005)
  • Yunnan provincial innovation team project (Award 2015HC030)
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001147
2018-09-25
2024-12-07
Loading full text...

Full text loading...

/deliver/fulltext/jgv/101/9/972.html?itemId=/content/journal/jgv/10.1099/jgv.0.001147&mimeType=html&fmt=ahah

References

  1. Smith JM, Uvin AZ, Macmadu A, Rich JD. Epidemiology and treatment of hepatitis B in prisoners. Curr Hepatol Rep 2017; 16:178–183 [View Article][PubMed]
    [Google Scholar]
  2. Nosratabadi R, Alavian SM, Zare-Bidaki M, Shahrokhi VM, Arababadi MK. Innate immunity related pathogen recognition receptors and chronic hepatitis B infection. Mol Immunol 2017; 90:64–73 [View Article][PubMed]
    [Google Scholar]
  3. Hong X, Kim ES, Guo H. Epigenetic regulation of hepatitis B virus covalently closed circular DNA: Implications for epigenetic therapy against chronic hepatitis B. Hepatology 2017; 66:2066–2077 [View Article][PubMed]
    [Google Scholar]
  4. Lee SY, Lee SH, Kim JE, Kim H, Kim K et al. Identification of novel A2/C2 inter-genotype recombinants of hepatitis B virus from a korean chronic patient co-infected with both genotype A2 and C2. Int J Mol Sci 2017; 18:737 [View Article][PubMed]
    [Google Scholar]
  5. Lin CL, Kao JH. Natural history of acute and chronic hepatitis B: the role of HBV genotypes and mutants. Best Pract Res Clin Gastroenterol 2017; 31:249–255 [View Article][PubMed]
    [Google Scholar]
  6. Ito K, Yoneda M, Sakamoto K, Mizokami M. Virological and clinical characteristics of hepatitis B virus genotype A. J Gastroenterol 2018; 53:18–26 [View Article][PubMed]
    [Google Scholar]
  7. Hübschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM et al. Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect 2011; 17:88–94 [View Article][PubMed]
    [Google Scholar]
  8. Shi W, Zhu C, Zheng W, Carr MJ, Higgins DG et al. Subgenotype reclassification of genotype B hepatitis B virus. BMC Gastroenterol 2012; 12:116 [View Article][PubMed]
    [Google Scholar]
  9. Mulyanto, 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 [View Article][PubMed]
    [Google Scholar]
  10. Hundie GB, Stalin Raj V, Gebre Michael D, Pas SD, Koopmans MP et al. A novel hepatitis B virus subgenotype D10 circulating in Ethiopia. J Viral Hepat 2017; 24:163–173 [View Article][PubMed]
    [Google Scholar]
  11. Mojsiejczuk LN, Torres C, Pisano MB, Re V, Campos RH et al. New pieces on genetic diversity and evolutionary history of hepatitis B virus: characterization of the novel subgenotype F6. Infect Genet Evol 2017; 47:140–142 [View Article][PubMed]
    [Google Scholar]
  12. Shen T, Yan XM, Liu HX, Zhang BX, Li L et al. Genotype I of hepatitis B virus was found in east Xishuangbanna, China and molecular dynamics of HBV/I. J Viral Hepat 2015; 22:37–45 [View Article][PubMed]
    [Google Scholar]
  13. Araujo NM. Hepatitis B virus intergenotypic recombinants worldwide: an overview. Infect Genet Evol 2015; 36:500–510 [View Article][PubMed]
    [Google Scholar]
  14. Alonso S, Guerra AR, Carreira L, Ferrer , Gutiérrez ML et al. Upcoming pharmacological developments in chronic hepatitis B: can we glimpse a cure on the horizon?. BMC Gastroenterol 2017; 17:168 [View Article][PubMed]
    [Google Scholar]
  15. Liu J, Fan D. Hepatitis B in China. Lancet 2007; 369:1582–1583 [View Article][PubMed]
    [Google Scholar]
  16. Chang Y, Choe WH, Sinn DH, Lee JH, Ahn SH et al. Nucleos(t)ide analogue treatment for patients with hepatitis B virus (HBV) e antigen-positive chronic HBV genotype C infection: a nationwide, multicenter, retrospective study. J Infect Dis 2017; 216:1407–1414 [View Article][PubMed]
    [Google Scholar]
  17. Shen S, Liang X, Hamed K, Tanaka Y, Omagari K et al. Effect of hepatitis B virus subgenotype on antiviral response in nucleoside-treated hepatitis B envelope antigen-positive patients. Hepatol Res 2018; 48:134–143 [View Article][PubMed]
    [Google Scholar]
  18. Li HM, Wang JQ, Wang R, Zhao Q, Li L et al. Hepatitis B virus genotypes and genome characteristics in China. World J Gastroenterol 2015; 21:6684–6697 [View Article][PubMed]
    [Google Scholar]
  19. Wang B, Feng Y, Li Z, Duan H, Zhao T et al. Distribution and diversity of hepatitis B virus genotypes in Yunnan, China. J Med Virol 2014; 86:1675–1682 [View Article][PubMed]
    [Google Scholar]
  20. You J, Sriplung H, Chongsuvivatwong V, Geater A, Zhuang L et al. Profile, spectrum and significance of hepatitis B virus genotypes in chronic HBV-infected patients in Yunnan, China. Hepatobiliary Pancreat Dis Int 2008; 7:271–279[PubMed]
    [Google Scholar]
  21. Shen YY, Hou W, Yang ZQ, Xiao W. Hepatitis B virus infection and genotype in asymptomatic people from 10 ethnic groups in Yunnan, China. World J Gastroenterol 2015; 21:12586–12592 [View Article][PubMed]
    [Google Scholar]
  22. Nwe NW, Nakamoto S, Myint MS, Moriyama M, Kanda T et al. Hepatitis B virus genotype C is predominant in Myanmar. Diseases 2017; 6:3
    [Google Scholar]
  23. Huy TT, Ushijima H, Quang VX, Win KM, Luengrojanakul P et al. Genotype C of hepatitis B virus can be classified into at least two subgroups. J Gen Virol 2004; 85:283–292 [View Article][PubMed]
    [Google Scholar]
  24. Shi W, Zhang Z, Ling C, Zheng W, Zhu C et al. Hepatitis B virus subgenotyping: history, effects of recombination, misclassifications, and corrections. Infect Genet Evol 2013; 16:355–361 [View Article][PubMed]
    [Google Scholar]
  25. 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; 20:7152–7168 [View Article][PubMed]
    [Google Scholar]
  26. Castelhano N, Araujo NM, Arenas M. Heterogeneous recombination among Hepatitis B virus genotypes. Infect Genet Evol 2017; 54:486–490 [View Article][PubMed]
    [Google Scholar]
  27. Liaw YF. Therapy of chronic hepatitis B: current challenges and opportunities. J Viral Hepat 2002; 9:393–399 [View Article][PubMed]
    [Google Scholar]
  28. Huy TT, Abe K. Molecular epidemiology of hepatitis B and C virus infections in Asia. Pediatr Int 2004; 46:223–230 [View Article][PubMed]
    [Google Scholar]
  29. Günther S, Li BC, Miska S, Krüger DH, Meisel H et al. A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. J Virol 1995; 69:5437–5444[PubMed]
    [Google Scholar]
  30. Günther S, Sommer G, von Breunig F, Iwanska A, Kalinina T et al. Amplification of full-length hepatitis B virus genomes from samples from patients with low levels of viremia: frequency and functional consequences of PCR-introduced mutations. J Clin Microbiol 1998; 36:531[PubMed]
    [Google Scholar]
/content/journal/jgv/10.1099/jgv.0.001147
Loading
/content/journal/jgv/10.1099/jgv.0.001147
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
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