Next-generation sequencing analysis of new genotypes appearing during antiviral treatment of chronic hepatitis C reveals that these are selected from pre-existing minor strains Open Access

Abstract

Coinfection with more than one hepatitis C virus (HCV) genotype is common, but its dynamics, particularly during antiviral treatment, remain largely unknown. We employed next-generation sequencing (NGS) to analyse sequential serum and peripheral blood mononuclear cell (PBMC) samples in seven patients with transient presence or permanent genotype change during antiviral treatment with interferon and ribavirin. Specimens were collected right before the therapy initiation and at 2, 4, 6, 8, 12, 20, 24, 36, 44 and 48 weeks during treatment and 6 months after treatment ceased. A mixture of two different genotypes was detected in the pretreatment samples from five patients and the minor genotype constituted 0.02 to 38 %. A transient or permanent change of the predominant genotype was observed in six patients. In three cases genotype 3 was replaced as the predominant genotype by genotype 4, in two cases genotype 3 was replaced by genotype 1, and in one subject genotype 1 was replaced by genotype 4. The PBMC- and serum-derived sequences were frequently discordant with respect to genotype and/or genotype proportions. In conclusion, pre-existing minor HCV genotypes can be selected rapidly during antiviral treatment and become transiently or permanently predominant. In coinfections involving genotype 3, genotype 3 was eliminated first from both the serum and PBMC compartments. The PBMC- and serum-derived HCV sequences were frequently discordant with respect to genotype and/or genotype proportions, suggesting that they constitute separate compartments with their own dynamics.

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2018-11-05
2024-03-29
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References

  1. Contreras AM, Hiasa Y, He W, Terella A, Schmidt EV et al. Viral RNA mutations are region specific and increased by ribavirin in a full-length hepatitis C virus replication system. J Virol 2002; 76:8505–8517 [View Article][PubMed]
    [Google Scholar]
  2. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282:103–107 [View Article][PubMed]
    [Google Scholar]
  3. Messina JP, Pigott DM, Golding N, Duda KA, Brownstein JS et al. The global distribution of Crimean-Congo hemorrhagic fever. Trans R Soc Trop Med Hyg 2015; 109:503–513 [View Article][PubMed]
    [Google Scholar]
  4. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 2014; 59:318–327 [View Article][PubMed]
    [Google Scholar]
  5. Simmonds P. Variability of hepatitis C virus. Hepatology 1995; 21:570–583 [View Article][PubMed]
    [Google Scholar]
  6. Blackard JT, Hiasa Y, Smeaton L, Jamieson DJ, Rodriguez I et al. Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection. J Infect Dis 2007; 195:1765–1773 [View Article][PubMed]
    [Google Scholar]
  7. Domingo E, Gomez J. Quasispecies and its impact on viral hepatitis. Virus Res 2007; 127:131–150 [View Article][PubMed]
    [Google Scholar]
  8. Forns X, Purcell RH, Bukh J. Quasispecies in viral persistence and pathogenesis of hepatitis C virus. Trends Microbiol 1999; 7:402–410 [View Article][PubMed]
    [Google Scholar]
  9. Sheridan I, Pybus OG, Holmes EC, Klenerman P. High-resolution phylogenetic analysis of hepatitis C virus adaptation and its relationship to disease progression. J Virol 2004; 78:3447–3454 [View Article][PubMed]
    [Google Scholar]
  10. Rong L, Dahari H, Ribeiro RM, Perelson AS. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010; 2:30ra32 [View Article][PubMed]
    [Google Scholar]
  11. Deutsch M, Hadziyannis SJ. Old and emerging therapies in chronic hepatitis C: an update. J Viral Hepat 2008; 15:2–11 [View Article][PubMed]
    [Google Scholar]
  12. Laskus T, Wang LF, Radkowski M, Nowicki M, Wilkinson J et al. Exposure of hepatitis C virus-negative recipients to > or =2 infected blood donors. J Infect Dis 2001; 183:666–669 [View Article][PubMed]
    [Google Scholar]
  13. Laskus T, Radkowski M, Wilkinson J, Vargas H, Rakela J. The origin of hepatitis C virus reinfecting transplanted livers: serum-derived versus peripheral blood mononuclear cell-derived virus. J Infect Dis 2002; 185:417–421 [View Article][PubMed]
    [Google Scholar]
  14. Chung E, Ferns RB, He M, Rigatti R, Grant P et al. Ultra-deep sequencing provides insights into the virology of hepatitis C super-infections in a case of three sequential infections with different genotypes. J Clin Virol 2015; 70:63–66 [View Article][PubMed]
    [Google Scholar]
  15. Aitken CK, Tracy SL, Revill P, Bharadwaj M, Bowden DS et al. Consecutive infections and clearances of different hepatitis C virus genotypes in an injecting drug user. J Clin Virol 2008; 41:293–296 [View Article][PubMed]
    [Google Scholar]
  16. Ramachandran S, Campo DS, Dimitrova ZE, Xia GL, Purdy MA et al. Temporal variations in the hepatitis C virus intrahost population during chronic infection. J Virol 2011; 85:6369–6380 [View Article][PubMed]
    [Google Scholar]
  17. Uebelhoer L, Han JH, Callendret B, Mateu G, Shoukry NH et al. Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness. PLoS Pathog 2008; 4:e1000143 [View Article][PubMed]
    [Google Scholar]
  18. Chueca N, Rivadulla I, Lovatti R, Reina G, Blanco A et al. Using NS5B sequencing for hepatitis c virus genotyping reveals discordances with commercial platforms. PLoS One 2016; 11:e0153754 [View Article][PubMed]
    [Google Scholar]
  19. Tsubota A, Fujise K, Namiki Y, Tada N. Peginterferon and ribavirin treatment for hepatitis C virus infection. World J Gastroenterol 2011; 17:419–432 [View Article][PubMed]
    [Google Scholar]
  20. Boutabout M, Wilhelm M, Wilhelm FX. DNA synthesis fidelity by the reverse transcriptase of the yeast retrotransposon Ty1. Nucleic Acids Res 2001; 29:2217–2222 [View Article][PubMed]
    [Google Scholar]
  21. Eckert KA, Kunkel TA. High fidelity DNA synthesis by the Thermus aquaticus DNA polymerase. Nucleic Acids Res 1990; 18:3739–3744 [View Article][PubMed]
    [Google Scholar]
  22. Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE et al. Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol 2012; 30:434–439 [View Article][PubMed]
    [Google Scholar]
  23. Giannini C, Giannelli F, Monti M, Careccia G, Marrocchi ME et al. Prevalence of mixed infection by different hepatitis C virus genotypes in patients with hepatitis C virus-related chronic liver disease. J Lab Clin Med 1999; 134:68–73 [View Article][PubMed]
    [Google Scholar]
  24. Nainan OV, Lu L, Gao FX, Meeks E, Robertson BH et al. Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees. J Gen Virol 2006; 87:83–91 [View Article][PubMed]
    [Google Scholar]
  25. Buoro S, Pizzighella S, Boschetto R, Pellizzari L, Cusan M et al. Typing of hepatitis C virus by a new method based on restriction fragment length polymorphism. Intervirology 1999; 42:1–8 [View Article][PubMed]
    [Google Scholar]
  26. Cai Q, Zhao Z, Liu Y, Shao X, Gao Z. Comparison of three different HCV genotyping methods: core, NS5B sequence analysis and line probe assay. Int J Mol Med 2013; 31:347–352 [View Article][PubMed]
    [Google Scholar]
  27. Qiu P, Stevens R, Wei B, Lahser F, Howe AY et al. HCV genotyping from NGS short reads and its application in genotype detection from HCV mixed infected plasma. PLoS One 2015; 10:e0122082 [View Article][PubMed]
    [Google Scholar]
  28. Micalessi MI, Gérard C, Ameye L, Plasschaert S, Brochier B et al. Distribution of hepatitis C virus genotypes among injecting drug users in contact with treatment centers in Belgium, 2004-2005. J Med Virol 2008; 80:640–645 [View Article][PubMed]
    [Google Scholar]
  29. Bagaglio S, Uberti-Foppa C, di Serio C, Trentini F, Andolina A et al. Dynamic of mixed HCV Infection in plasma and PBMC of HIV/HCV patients under treatment with Peg-IFN/Ribavirin. Medicine 2015; 94:e1876 [View Article][PubMed]
    [Google Scholar]
  30. Cunningham EB, Applegate TL, Lloyd AR, Dore GJ, Grebely J. Mixed HCV infection and reinfection in people who inject drugs-impact on therapy. Nat Rev Gastroenterol Hepatol 2015; 12:218–230 [View Article][PubMed]
    [Google Scholar]
  31. Farci P, Alter HJ, Govindarajan S, Wong DC, Engle R et al. Lack of protective immunity against reinfection with hepatitis C virus. Science 1992; 258:135–140 [View Article][PubMed]
    [Google Scholar]
  32. Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006; 55:1350–1359 [View Article][PubMed]
    [Google Scholar]
  33. Laskus T, Radkowski M, Wang LF, Jang SJ, Vargas H et al. Hepatitis C virus quasispecies in patients infected with HIV-1: correlation with extrahepatic viral replication. Virology 1998; 248:164–171 [View Article][PubMed]
    [Google Scholar]
  34. Pal S, Sullivan DG, Kim S, Lai KK, Kae J et al. Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: implications of HCV lymphotropism. Gastroenterology 2006; 130:1107–1116 [View Article][PubMed]
    [Google Scholar]
  35. Laskus T, Radkowski M, Jablonska J, Kibler K, Wilkinson J et al. Human immunodeficiency virus facilitates infection/replication of hepatitis C virus in native human macrophages. Blood 2004; 103:3854–3859 [View Article][PubMed]
    [Google Scholar]
  36. Radkowski M, Gallegos-Orozco JF, Jablonska J, Colby TV, Walewska-Zielecka B et al. Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology 2005; 41:106–114 [View Article][PubMed]
    [Google Scholar]
  37. Buckton AJ, Ngui SL, Arnold C, Boast K, Kovacs J et al. Multitypic hepatitis C virus infection identified by real-time nucleotide sequencing of minority genotypes. J Clin Microbiol 2006; 44:2779–2784 [View Article][PubMed]
    [Google Scholar]
  38. Malboeuf CM, Yang X, Charlebois P, Qu J, Berlin AM et al. Complete viral RNA genome sequencing of ultra-low copy samples by sequence-independent amplification. Nucleic Acids Res 2013; 41:e13 [View Article][PubMed]
    [Google Scholar]
  39. Bukowska-Ośko I, Pawełczyk A, Perlejewski K, Kubisa N, Caraballo Cortés K et al. Genetic variability of hepatitis C virus (HCV) 5' Untranslated Region in HIV/HCV coinfected patients treated with pegylated interferon and ribavirin. PLoS One 2015; 10:e0125604 [View Article][PubMed]
    [Google Scholar]
  40. Laskus T, Radkowski M, Wang LF, Nowicki M, Rakela J. Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication. J Virol 2000; 74:1014–1017 [View Article][PubMed]
    [Google Scholar]
  41. Caraballo Cortes K, Bukowska-Ośko I, Pawełczyk A, Perlejewski K, Płoski R et al. Next-generation sequencing of 5' untranslated region of hepatitis C virus in search of minor viral variant in a patient who revealed new genotype while on antiviral treatment. Adv Exp Med Biol 2016; 885:11–23 [View Article][PubMed]
    [Google Scholar]
  42. Ghany MG, Strader DB, Thomas DL, Seeff LB. American association for the study of liver d. diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335–1374
    [Google Scholar]
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