1887

Abstract

Hepatitis C virus (HCV) exists as a quasispecies within an infected individual. We have previously reported an in-frame 3 bp insertion event at the N-terminal region of the E2 glycoprotein from a genotype 4a HCV isolate giving rise to an atypical 28 aa hypervariable region (HVR) 1. To further explore quasispecies evolution at the HVR1, serum samples collected over 9.6 years from the same chronically infected, treatment naïve individual were subjected to retrospective clonal analysis. Uniquely, we observed that isolates containing this atypical HVR1 not only persisted for 7.6 years, but dominated the quasispecies swarm. Just as striking was the collapse of this population of variants towards the end of the sampling period in synchrony with variants containing a classical HVR1 from the same lineage. The replication space was subsequently occupied by a second minor lineage, which itself was only intermittently detectable at earlier sampling points. In conjunction with the observed genetic shift, the coexistence of two distinct HVR1 populations facilitated the detection of putative intra-subtype recombinants, which included the identification of the likely ancestral parental donors. Juxtaposed to the considerable plasticity of the HVR1, we also document a degree of mutational inflexibility as each of the HVR1 subpopulations within our dataset exhibited overall genetic conservation and convergence. Finally, we raise the issue of genetic analysis in the context of mixed lineage infections.

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2012-12-01
2022-01-20
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References

  1. Abe K., Inchauspe G., Fujisawa K. 1992; Genomic characterization and mutation rate of hepatitis C virus isolated from a patient who contracted hepatitis during an epidemic of non-A, non-B hepatitis in Japan. J Gen Virol 73:2725–2729 [View Article][PubMed]
    [Google Scholar]
  2. Aizaki H., Saito A., Kusakawa I., Ashiwara Y., Nagamori S., Toda G., Suzuki T., Ishii K., Matsuura Y., Miyamura T. 1996; Mother-to-child transmission of a hepatitis C virus variant with an insertional mutation in its hypervariable region. J Hepatol 25:608–613 [View Article][PubMed]
    [Google Scholar]
  3. Arbiza J., Mirazo S., Fort H. 2010; Viral quasispecies profiles as the result of the interplay of competition and cooperation. BMC Evol Biol 10:137 [View Article][PubMed]
    [Google Scholar]
  4. Austermann-Busch S., Becher P. 2012; RNA structural elements determine frequency and sites of nonhomologous recombination in an animal plus-strand RNA virus. J Virol 86:7393–7402 [View Article][PubMed]
    [Google Scholar]
  5. Bankwitz D., Steinmann E., Bitzegeio J., Ciesek S., Friesland M., Herrmann E., Zeisel M. B., Baumert T. F., Keck Z. Y.other authors 2010; Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. J Virol 84:5751–5763 [View Article][PubMed]
    [Google Scholar]
  6. Briones C., Bastolla U. 2005; Protein evolution in viral quasispecies under selective pressure: a thermodynamic and phylogenetic analysis. Gene 347:237–246 [View Article][PubMed]
    [Google Scholar]
  7. Brown R. J., Juttla V. S., Tarr A. W., Finnis R., Irving W. L., Hemsley S., Flower D. R., Borrow P., Ball J. K. 2005; Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection. J Gen Virol 86:1931–1942 [View Article][PubMed]
    [Google Scholar]
  8. Campo D. S., Dimitrova Z., Yokosawa J., Hoang D., Perez N. O., Ramachandran S., Khudyakov Y. 2012; Hepatitis C virus antigenic convergence. Sci Rep 2:267 [View Article][PubMed]
    [Google Scholar]
  9. Chang M., Marquardt A. P., Wood B. L., Williams O., Cotler S. J., Taylor S. L., Carithers R. L. Jr, Gretch D. R. 2000; In situ distribution of hepatitis C virus replicative-intermediate RNA in hepatic tissue and its correlation with liver disease. J Virol 74:944–955 [View Article][PubMed]
    [Google Scholar]
  10. Cuevas J. M., Torres-Puente M., Jiménez-Hernández N., Bracho M. A., García-Robles I., Carnicer F., Olmo J. D., Ortega E., González-Candelas F., Moya A. 2009; Combined therapy of interferon plus ribavirin promotes multiple adaptive solutions in hepatitis C virus. J Med Virol 81:650–656 [View Article][PubMed]
    [Google Scholar]
  11. Domingo E., Martin V., Perales C., Grande-Pérez A., García-Arriaza J., Arias A. 2006; Viruses as quasispecies: biological implications. Curr Top Microbiol Immunol 299:51–82 [View Article][PubMed]
    [Google Scholar]
  12. Duffy S., Shackelton L. A., Holmes E. C. 2008; Rates of evolutionary change in viruses: patterns and determinants. Nat Rev Genet 9:267–276 [View Article][PubMed]
    [Google Scholar]
  13. Farci P., Shimoda A., Wong D., Cabezon T., De Gioannis D., Strazzera A., Shimizu Y., Shapiro M., Alter H. J., Purcell R. H. 1996; Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc Natl Acad Sci U S A 93:15394–15399 [View Article][PubMed]
    [Google Scholar]
  14. Gerotto M., Dal Pero F., Loffreda S., Bianchi F. B., Alberti A., Lenzi M. 2001; A 385 insertion in the hypervariable region 1 of hepatitis C virus E2 envelope protein is found in some patients with mixed cryoglobulinemia type 2. Blood 98:2657–2663 [View Article][PubMed]
    [Google Scholar]
  15. González-Candelas F., López-Labrador F. X., Bracho M. A. 2011; Recombination in hepatitis C virus. Viruses 3:2006–2024 [View Article][PubMed]
    [Google Scholar]
  16. Hino K., Korenaga M., Orito E., Katoh Y., Yamaguchi Y., Ren F., Kitase A., Satoh Y., Fujiwara D., Okita K. 2002; Constrained genomic and conformational variability of the hypervariable region 1 of hepatitis C virus in chronically infected patients. J Viral Hepat 9:194–201 [View Article][PubMed]
    [Google Scholar]
  17. Höhne M., Schreier E., Roggendorf M. 1994; Sequence variability in the env-coding region of hepatitis C virus isolated from patients infected during a single source outbreak. Arch Virol 137:25–34 [View Article][PubMed]
    [Google Scholar]
  18. Kato N., Ootsuyama Y., Tanaka T., Nakagawa M., Nakazawa T., Muraiso K., Ohkoshi S., Hijikata M., Shimotohno K. 1992; Marked sequence diversity in the putative envelope proteins of hepatitis C viruses. Virus Res 22:107–123 [View Article][PubMed]
    [Google Scholar]
  19. Kato N., Sekiya H., Ootsuyama Y., Nakazawa T., Hijikata M., Ohkoshi S., Shimotohno K. 1993; Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus. J Virol 67:3923–3930[PubMed]
    [Google Scholar]
  20. Krey T., d’Alayer J., Kikuti C. M., Saulnier A., Damier-Piolle L., Petitpas I., Johansson D. X., Tawar R. G., Baron B.other authors 2010; The disulfide bonds in glycoprotein E2 of hepatitis C virus reveal the tertiary organization of the molecule. PLoS Pathog 6:e1000762 [View Article][PubMed]
    [Google Scholar]
  21. Kuiken C., Yusim K., Boykin L., Richardson R. 2005; The Los Alamos hepatitis C sequence database. Bioinformatics 21:379–384 [View Article][PubMed]
    [Google Scholar]
  22. Kwok S., Higuchi R. 1989; Avoiding false positives with PCR. Nature 339:237–238 [View Article][PubMed]
    [Google Scholar]
  23. Lehmann M., Meyer M. F., Monazahian M., Tillmann H. L., Manns M. P., Wedemeyer H. 2004; High rate of spontaneous clearance of acute hepatitis C virus genotype 3 infection. J Med Virol 73:387–391 [View Article][PubMed]
    [Google Scholar]
  24. Lin H. J., Seeff L. B., Barbosa L., Hollinger F. B. 2001; Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: divergence over time. Hepatology 34:424–429 [View Article][PubMed]
    [Google Scholar]
  25. Livingstone C. D., Barton G. J. 1993; Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation. Comput Appl Biosci 9:745–756[PubMed]
    [Google Scholar]
  26. Logvinoff C., Major M. E., Oldach D., Heyward S., Talal A., Balfe P., Feinstone S. M., Alter H., Rice C. M., McKeating J. A. 2004; Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc Natl Acad Sci U S A 101:10149–10154 [View Article][PubMed]
    [Google Scholar]
  27. Lole K. S., Bollinger R. C., Paranjape R. S., Gadkari D., Kulkarni S. S., Novak N. G., Ingersoll R., Sheppard H. W., Ray S. C. 1999; Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160[PubMed]
    [Google Scholar]
  28. Luciani F., Alizon S. 2009; The evolutionary dynamics of a rapidly mutating virus within and between hosts: the case of hepatitis C virus. PLOS Comput Biol 5:e1000565 [View Article][PubMed]
    [Google Scholar]
  29. McCaffrey K., Gouklani H., Boo I., Poumbourios P., Drummer H. E. 2011; The variable regions of hepatitis C virus glycoprotein E2 have an essential structural role in glycoprotein assembly and virion infectivity. J Gen Virol 92:112–121 [View Article][PubMed]
    [Google Scholar]
  30. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. 1989; Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell 58:901–910 [View Article][PubMed]
    [Google Scholar]
  31. Moreau I., Levis J., Crosbie O., Kenny-Walsh E., Fanning L. J. 2008a; Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a. Virol J 5:78 [View Article][PubMed]
    [Google Scholar]
  32. Moreau I., O’Sullivan H., Murray C., Levis J., Crosbie O., Kenny-Walsh E., Fanning L. J. 2008b; Separation of hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile. Virol J 5:103 [View Article][PubMed]
    [Google Scholar]
  33. Morel V., Descamps V., François C., Fournier C., Brochot E., Capron D., Duverlie G., Castelain S. 2010; Emergence of a genomic variant of the recombinant 2k/1b strain during a mixed hepatitis C infection: a case report. J Clin Virol 47:382–386 [View Article][PubMed]
    [Google Scholar]
  34. Morel V., Fournier C., François C., Brochot E., Helle F., Duverlie G., Castelain S. 2011; Genetic recombination of the hepatitis C virus: clinical implications. J Viral Hepat 18:77–83 [View Article][PubMed]
    [Google Scholar]
  35. Moreno M. P., Casane D., López L., Cristina J. 2006; Evidence of recombination in quasispecies populations of a hepatitis C virus patient undergoing anti-viral therapy. Virol J 3:87 [View Article][PubMed]
    [Google Scholar]
  36. Mullan B., Kenny-Walsh E., Collins J. K., Shanahan F., Fanning L. J. 2001; Inferred hepatitis C virus quasispecies diversity is influenced by choice of DNA polymerase in reverse transcriptase-polymerase chain reactions. Anal Biochem 289:137–146 [View Article][PubMed]
    [Google Scholar]
  37. Murphy D., Chamberland J., Dandavino R., Sablon E. 2007; A new genotype of hepatitis C virus originating from central Africa. Hepatology 46:623a
    [Google Scholar]
  38. Nadarajah R., Khan G. Y., Miller S. A., Brooks G. F. 2007; Evaluation of a new-generation line-probe assay that detects 5′ untranslated and core regions to genotype and subtype hepatitis C virus. Am J Clin Pathol 128:300–304 [View Article][PubMed]
    [Google Scholar]
  39. Pawlotsky J. M. 2006; Hepatitis C virus population dynamics during infection. Curr Top Microbiol Immunol 299:261–284 [View Article][PubMed]
    [Google Scholar]
  40. Penin F., Combet C., Germanidis G., Frainais P. O., Deléage G., Pawlotsky J. M. 2001; Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment. J Virol 75:5703–5710 [View Article][PubMed]
    [Google Scholar]
  41. Penin F., Dubuisson J., Rey F. A., Moradpour D., Pawlotsky J. M. 2004; Structural biology of hepatitis C virus. Hepatology 39:5–19 [View Article][PubMed]
    [Google Scholar]
  42. Polyak S. J., Faulkner G., Carithers R. L. Jr, Corey L., Gretch D. R. 1997; Assessment of hepatitis C virus quasispecies heterogeneity by gel shift analysis: correlation with response to interferon therapy. J Infect Dis 175:1101–1107 [View Article][PubMed]
    [Google Scholar]
  43. Posada D. 2008; jModelTest: phylogenetic model averaging. Mol Biol Evol 25:1253–1256 [View Article][PubMed]
    [Google Scholar]
  44. Sallie R. 2005; Replicative homeostasis: a fundamental mechanism mediating selective viral replication and escape mutation. Virol J 2:10 [View Article][PubMed]
    [Google Scholar]
  45. Schmidt-Martin D., Crosbie O., Kenny-Walsh E., Fanning L. J. 2012; Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase. Virus Adaptation and Treatment 4:43–50 [View Article]
    [Google Scholar]
  46. Sentandreu V., Jiménez-Hernández N., Torres-Puente M., Bracho M. A., Valero A., Gosalbes M. J., Ortega E., Moya A., González-Candelas F. 2008; Evidence of recombination in intrapatient populations of hepatitis C virus. PLoS ONE 3:e3239 [View Article][PubMed]
    [Google Scholar]
  47. Shi W., Freitas I. T., Zhu C., Zheng W., Hall W. W., Higgins D. G. 2012; Recombination in hepatitis C virus: identification of four novel naturally occurring inter-subtype recombinants. PLoS ONE 7:e41997 [View Article][PubMed]
    [Google Scholar]
  48. Simmonds P. 2004; Genetic diversity and evolution of hepatitis C virus – 15 years on. J Gen Virol 85:3173–3188 [View Article][PubMed]
    [Google Scholar]
  49. Simmonds P., Tuplin A., Evans D. J. 2004; Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: implications for virus evolution and host persistence. RNA 10:1337–1351 [View Article][PubMed]
    [Google Scholar]
  50. Simmonds P., Bukh J., Combet C., Deléage G., Enomoto N., Feinstone S., Halfon P., Inchauspé G., Kuiken C.other authors 2005; Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42:962–973 [View Article][PubMed]
    [Google Scholar]
  51. Simon-Loriere E., Martin D. P., Weeks K. M., Negroni M. 2010; RNA structures facilitate recombination-mediated gene swapping in HIV-1. J Virol 84:12675–12682 [View Article][PubMed]
    [Google Scholar]
  52. Tamura K., Peterson D., Peterson N., Stecher G., Nei M., Kumar S. 2011; mega5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739 [View Article][PubMed]
    [Google Scholar]
  53. Timm J., Roggendorf M. 2007; Sequence diversity of hepatitis C virus: implications for immune control and therapy. World J Gastroenterol 13:4808–4817[PubMed]
    [Google Scholar]
  54. Torres-Puente M., Cuevas J. M., Jiménez-Hernández N., Bracho M. A., García-Robles I., Carnicer F., del Olmo J., Ortega E., Moya A., González-Candelas F. 2007; Contribution of insertions and deletions to the variability of hepatitis C virus populations. J Gen Virol 88:2198–2203 [View Article][PubMed]
    [Google Scholar]
  55. Troesch M., Meunier I., Lapierre P., Lapointe N., Alvarez F., Boucher M., Soudeyns H. 2006; Study of a novel hypervariable region in hepatitis C virus (HCV) E2 envelope glycoprotein. Virology 352:357–367 [View Article][PubMed]
    [Google Scholar]
  56. Tuplin A., Struthers M., Simmonds P., Evans D. J. 2012; A twist in the tail: SHAPE mapping of long-range interactions and structural rearrangements of RNA elements involved in HCV replication. Nucleic Acids Res 40:6908–6921 [View Article][PubMed]
    [Google Scholar]
  57. von Hahn T., Yoon J. C., Alter H., Rice C. M., Rehermann B., Balfe P., McKeating J. A. 2007; Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 132:667–678 [View Article][PubMed]
    [Google Scholar]
  58. Wang X. H., Netski D. M., Astemborski J., Mehta S. H., Torbenson M. S., Thomas D. L., Ray S. C. 2007; Progression of fibrosis during chronic hepatitis C is associated with rapid virus evolution. J Virol 81:6513–6522 [View Article][PubMed]
    [Google Scholar]
  59. Zaphiropoulos P. G. 2002; Template switching generated during reverse transcription?. FEBS Lett 527:326 [View Article][PubMed]
    [Google Scholar]
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