1887

Abstract

Analysis of complete polyprotein-encoding sequences of hepatitis C virus genotype 1b (HCV-1b) showed evidence not only of past purifying selection but also of abundant slightly deleterious non-synonymous variants subject to ongoing purifying selection. The NS3 protein (with protease and NTPase/helicase activity) revealed less evidence of purifying selection acting on the cytotoxic T cells (CTL) epitopes than did the other proteins, whereas outside the CTL epitopes NS3 was more conserved than the other proteins. Moreover, NS3 showed a high incidence of forward-and-backward or parallel non-synonymous changes in CTL epitopes, as measured by the consistency index across the phylogeny of HCV-1b genomes computed at non-singleton non-synonymous polymorphic sites. This result implies that certain non-synonymous mutations have recurred frequently throughout the phylogeny in the codons encoding the epitopes in NS3. This pattern is most easily explained by the frequent re-occurrence of the same set of escape mutations in CTL epitopes of NS3, which are selectively favoured within hosts expressing the presenting class I major histocompatibility complex molecule, but are subject to purifying selection at the population level. The fact that this pattern is most strikingly observed in the case of NS3 suggests that the evolutionary conflict between immune escape and functional constraint on the protein is more acute in the case of NS3 than any of the other proteins of HCV-1b.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/000992-0
2008-08-01
2020-07-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/8/1921.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/000992-0&mimeType=html&fmt=ahah

References

  1. Alter M. J. 2007; Epidemiology of hepatitis C virus infection. World J Gastroenterol 13:2436–2441 [CrossRef]
    [Google Scholar]
  2. Cox A. L., Mosbruger T., Mao Q., Liu Z., Wang X.-H., Yang H.-C., Sidney J., Sette A., Pardoll D. other authors 2005; Cellular immune selection with hepatitis C virus persistence in humans. J Exp Med 201:1741–1752 [CrossRef]
    [Google Scholar]
  3. Dunn O. J. 1964; Multiple comparisons using rank sums. Technometrics 6:241–252 [CrossRef]
    [Google Scholar]
  4. Erickson A. L., Kimura Y., Igarashi S., Eichelberger J., Houghton M., Sidney J., McKinney D., Sette A., Hughes A. L., Walker C. M. 2001; The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 15:883–895 [CrossRef]
    [Google Scholar]
  5. Felsenstein J. 1985; Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791 [CrossRef]
    [Google Scholar]
  6. Gaudieri S., Rauch A., Park L. P., Freitas E., Herrmann S., Jeffrey G., Cheng W., Pfafferrott K., Naidoo K. other authors 2006; Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection. J Virol 80:11094–11104 [CrossRef]
    [Google Scholar]
  7. Gerlach J. T., Ulsenheimer A., Grüner N. H., Jung M.-C., Schraut W., Schirren C.-A., Heeg M., Scholz S., Witter K. other authors 2005; Minimal Tc-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4+ T-cell epitopes within hepatitis C virus NS3 and NS4 epitopes. J Virol 79:12425–12433 [CrossRef]
    [Google Scholar]
  8. Guglietta S., Garbuglia A. R., Pacciani V., Scottà C., Perrone M. P., Laurenti L., Spada E., Mele A., Capobianchi M. R. other authors 2005; Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection. Eur J Immunol 35:2627–2637 [CrossRef]
    [Google Scholar]
  9. Guo H.-Z., Yin Y., Wang W.-L., Zhang C.-S., Wang T., Wang Z., Zhang J., Cheng H., Wang H.-T. 2004; Sequence evolution of putative cytotoxic T cell epitopes in NS3 region of hepatitis C virus. World J Gastroenterol 10:847–851
    [Google Scholar]
  10. Hollander M., Wolfe D. A. 1973 Nonparametric Statistical Methods New York: Wiley & Sons;
    [Google Scholar]
  11. Hughes A. L. 1999 Adaptive Evolution of Genes and Genomes New York: Oxford University Press;
    [Google Scholar]
  12. Hughes A. L. 2005; Evidence for abundant slightly deleterious polymorphisms in bacterial populations. Genetics 169:533–538 [CrossRef]
    [Google Scholar]
  13. Hughes A. L. 2007a; Micro-scale signature of purifying selection in Marburg Virus genomes. Gene 392:266–272 [CrossRef]
    [Google Scholar]
  14. Hughes A. L. 2007b; Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level. Heredity 99:364–373 [CrossRef]
    [Google Scholar]
  15. Hughes A. L., French J. O. 2007; Homologous recombination and the pattern of nucleotide substitution in Ehrlichia ruminantium . Gene 387:31–37 [CrossRef]
    [Google Scholar]
  16. Hughes A. L., Hughes M. A. 2007; More effective purifying selection in RNA viruses than in DNA viruses. Gene 404:117–125 [CrossRef]
    [Google Scholar]
  17. Hughes A. L., Piontkivska H. 2008; Nucleotide sequence polymorphism in circoviruses. Infect Genet Evol 8:130–138 [CrossRef]
    [Google Scholar]
  18. Hughes A. L., Packer B., Welch R., Bergen A. W., Chanock S. J., Yeager M. 2003; Widespread purifying selection at polymorphic sites in human protein-coding loci. Proc Natl Acad Sci U S A 100:15754–15757 [CrossRef]
    [Google Scholar]
  19. Hughes A. L., Friedman R., Glenn N. L. 2006; The future of data analysis in evolutionary genomics. Curr Genomics 7:227–234 [CrossRef]
    [Google Scholar]
  20. Hughes A. L., Hughes M. A., Friedman R. 2007; Variable intensity of purifying selection on cytotoxic T-lymphocyte epitopes in hepatitis C virus. Virus Res 123:147–153 [CrossRef]
    [Google Scholar]
  21. Kimura M. 1977; Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 267:275–276 [CrossRef]
    [Google Scholar]
  22. Kuiken C., Yusim K., Boykin L., Richardson R. 2005; The Los Alamos HCV sequence database. Bioinformatics 21:379–384 [CrossRef]
    [Google Scholar]
  23. Kumar S., Tamura K., Nei M. 2004; mega3: integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5:150–163 [CrossRef]
    [Google Scholar]
  24. Kuntzen T., Timm J., Berical A., Lewis-Ximenez L. L., Jones A., Nolan B., , Schulze zur Wiesch J., Li B., Scheidewind A. other authors 2007; Viral sequence evolution in acute hepatitis C virus infection. J Virol 81:11658–11668 [CrossRef]
    [Google Scholar]
  25. Lauer G. M., Walker B. D. 2001; Hepatitis C virus infection. N Engl J Med 345:41–52 [CrossRef]
    [Google Scholar]
  26. Li W.-H. 1993; Unbiased estimates of the rates of synonymous and nonsynonymous substitution. J Mol Evol 36:96–99 [CrossRef]
    [Google Scholar]
  27. Muller R. 1996; The natural history of hepatitis C: clinical experiences. J Hepatol 24:52–54 [CrossRef]
    [Google Scholar]
  28. Nei M. 1987 Molecular Evolutionary Genetics New York: Columbia University Press;
    [Google Scholar]
  29. Nei M., Gojobori T. 1986; Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426
    [Google Scholar]
  30. Nei M., Kumar S. 2000 Molecular Evolution and Phylogenetics New York: Oxford University Press;
    [Google Scholar]
  31. Neumann-Haefelin C., Frick D. N., Wang J. J., Pybus O. G., Salloum S., Narula G. S., Eckart A., Biezynski A., Eiermann T. other authors 2008; Analysis of evolutionary forces in an immunodominant CD8 epitope in hepatitis C virus at a population level. J Virol 82:3438–3451 [CrossRef]
    [Google Scholar]
  32. Ohta T. 1973; Slightly deleterious mutant substitutions in evolution. Nature 246:96–98 [CrossRef]
    [Google Scholar]
  33. Parfieniuk A., Jaroszewicz J., Flisiak R. 2007; Specifically targeted antiviral therapy for hepatitis C virus. World J Gastroenterol 13:5673–5681 [CrossRef]
    [Google Scholar]
  34. Poon A. F., Pond S. L., Bennett P., Richman D. R., Leigh Brown A. J., Frost S. D. 2007; Adaptation to human populations is revealed by within-host polymorphisms in HIV-1 and hepatitis C virus. PLoS Pathog 3:e45 [CrossRef]
    [Google Scholar]
  35. Ray S. C., Fanning L., Wang X.-H., Netski D. M., Kenny-Walsh E., Thomas D. L. 2005; Divergent and convergent evolution after a common-source outbreak of hepatitis C virus. J Exp Med 201:1753–1759 [CrossRef]
    [Google Scholar]
  36. Saitou N., Nei M. 1987; The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425
    [Google Scholar]
  37. Seifert U., Liermann H., Racanelli V., Halenius A., Wiese M., Wedemeyer H., Ruppert T., Rispeter K., Henklein P. other authors 2004; Hepatitis C virus mutation affects proteasomal epitope processing. J Clin Invest 114:250–259 [CrossRef]
    [Google Scholar]
  38. Simmonds P., Bukh J., Combet C., Deléage G., Enomoto N., Feinstone S., Halfon P., Inschaupé G., Kuiken C. other authors 2005; Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42:962–973 [CrossRef]
    [Google Scholar]
  39. Söderholm J., Ahlén G., Kaul A., Frelin L., Alheim M., Barnfield C., Liljeström P., Weiland O., Milich D. R. other authors 2006; Relation between viral fitness and immune escape within the hepatitis C virus protease. Gut 55:266–274 [CrossRef]
    [Google Scholar]
  40. Suzuki T., Aizaki H., Murakami K., Shoji I., Wakita T. 2007; Molecular biology of hepatitis C virus. J Gastroenterol 42:411–423 [CrossRef]
    [Google Scholar]
  41. Swofford D. L. 2003 paup*: phylogenetic analysis using parsimony (and other methods), version 4 Sunderland, MA: Sinauer Associates;
    [Google Scholar]
  42. Tajima F. 1989; Statistical methods to test for nucleotide mutation hypothesis by DNA polymorphism. Genetics 123:585–595
    [Google Scholar]
  43. Tamura K., Dudley J., Nei M., Kumar S. 2007; mega4: molecular Evolutionary Genetics Analysis (mega) software version 4.0. Mol Biol Evol 24:1596–1599 [CrossRef]
    [Google Scholar]
  44. Tester I., Smyk-Pearson S., Wang P., Wertheimer A., Yao E., Lewinsohn D. M., Tavis J. E., Rosen H. R. 2005; Immune evasion versus recovery after acute hepatitis C virus infection from a shared source. J Exp Med 201:1725–1731 [CrossRef]
    [Google Scholar]
  45. Tian Y., Zhang H.-H., Wei L., Du S.-C., Chen H.-S., Fei R., Liu F. 2007; The functional evaluation of dendritic cell vaccines based on different hepatitits C virus nonstructural genes. Viral Immunol 20:553–561 [CrossRef]
    [Google Scholar]
  46. Timm J., Roggendorf M. 2007; Sequence diversity of hepatitis C virus: implications for immune control and therapy. World J Gastroenterol 13:4808–4817
    [Google Scholar]
  47. Timm J., Lauer G. M., Kavanagh D. G., Sheridan I., Kim A. Y., Lucas M., Pillay T., Ouchi K., Reyor L. L. other authors 2004; CD8 epitope escape and reversion in acute HCV infection. J Exp Med 200:1593–1604 [CrossRef]
    [Google Scholar]
  48. Timm J., Li B., Daniels M. G., Bhattacharya T., Reyor L. L., Allgaier R., Kuntzen T., Fischer W., Nolan B. E. other authors 2007; Human leukocyte antigen-associated sequence polymorphisms in hepatitis C virus reveal reproducible immune responses and constraints on viral evolution. Hepatology 46:339–349 [CrossRef]
    [Google Scholar]
  49. Wang H., Bian T., Merrill S. J., Eckels D. D. 2002; Sequence variation in the gene encoding the nonstructural 3 protein of hepatitis C virus: evidence for immune selection. J Mol Evol 54:465–473 [CrossRef]
    [Google Scholar]
  50. Weiner A., Erickson A. L., Kansopon J., Crawford K., Muchmore E., Hughes A. L., Houghton M., Walker C. M. 1995; Persistent hepatitis C virus infection in a chimpanzee is associated with the emergence of a cytotoxic T lymphocyte escape variant. Proc Natl Acad Sci U S A 92:2755–2759 [CrossRef]
    [Google Scholar]
  51. Yang Z., Nielsen R. 2000; Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. Mol Biol Evol 17:32–43 [CrossRef]
    [Google Scholar]
  52. Yusim K., Richardson R., Tao N., Szinger J., Funkhouser R., Korber B., Kuiken C. 2005; The Los Alamos hepatitis C immunology database. Appl Bioinformatics 4:217–225 [CrossRef]
    [Google Scholar]
  53. Zabaleta A., Llopiz D., Arribillage L., Silva L., Riezu-Boj J., Lasarte J. J., Borrás-Cuesta F., Prieto J., Sarobe P. 2008; Vaccination against hepatitis C virus with dendritic cells transduced with an adenovirus encoding NS3 protein. Mol Ther 16:210–217 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.2008/000992-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/000992-0
Loading

Data & Media loading...

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