1887

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Volume 86, Issue 7

Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection Free

Abstract

Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are important targets for the host immune response. The genes encoding these proteins exhibit a high degree of variability that gives rise to differing phenotypic traits, including alterations in receptor-binding affinity and immune recognition and escape. In order to elucidate patterns of adaptive evolution during chronic infection, a panel of full-length E1E2 clones was generated from sequential serum samples obtained from four chronically infected individuals. By using likelihood-based methods for phylogenetic inference, the evolutionary dynamics of circulating HCV quasispecies populations were assessed and a site-by-site analysis of the / ratio was performed, to identify specific codons undergoing diversifying positive selection. HCV phylogenies, coupled with the number and distribution of selected sites, differed markedly between patients, highlighting that HCV evolution during chronic infection is a patient-specific phenomenon. This analysis shows that purifying selection is the major force acting on HCV populations in chronic infection. Whilst no significant evidence for positive selection was observed in E1, a number of sites under positive selection were identified within the ectodomain of the E2 protein. All of these sites were located in regions hypothesized to be exposed to the selective environment of the host, including a number of functionally defined domains that have been reported to be involved in immune evasion and receptor binding. Dated-tip methods for estimation of underlying HCV mutation rates were also applied to the data, enabling prediction of the most recent common ancestor for each patient's quasispecies.

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2005-07-01
2024-04-23
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References

  1. Alfonso V., Flichman D. M., Sookoian S., Mbayed V. A., Campos R. H. 2004; Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection. J Gen Virol 85:39–46 [CrossRef]
     [Google Scholar]
  2. Allain J.-P., Dong Y., Vandamme A.-M., Moulton V., Salemi M. 2000; Evolutionary rate and genetic drift of hepatitis C virus are not correlated with the host immune response: studies of infected donor-recipient clusters. J Virol 74:2541–2549 [CrossRef]
     [Google Scholar]
  3. Allison S. L., Schalich J., Stiasny K., Mandl C. W., Heinz F. X. 2001; Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J Virol 75:4268–4275 [CrossRef]
     [Google Scholar]
  4. Alter M. J., Margolis H. S., Krawczynski K. other authors 1992; The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med 327:1899–1905 [CrossRef]
     [Google Scholar]
  5. Bartosch B., Vitelli A., Granier C. 7 other authors 2003; Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem 278:41624–41630 [CrossRef]
     [Google Scholar]
  6. Beaumont T., Quakkelaar E., van Nuenen A., Pantophlet R., Schuitemaker H. 2004; Increased sensitivity to CD4 binding site-directed neutralization following in vitro propagation on primary lymphocytes of a neutralization-resistant human immunodeficiency virus IIIB strain isolated from an accidentally infected laboratory worker. J Virol 78:5651–5657 [CrossRef]
     [Google Scholar]
  7. Booth J. C., Kumar U., Webster D., Monjardino J., Thomas H. C. 1998; Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients. Hepatology 27:223–227 [CrossRef]
     [Google Scholar]
  8. Brechot C., Nalpas B., Feitelson M. A. 1996; Interactions between alcohol and hepatitis viruses in the liver. Clin Lab Med 16:273–287
     [Google Scholar]
  9. Bukh J., Miller R. H., Purcell R. H. 1995; Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis 15:41–63 [CrossRef]
     [Google Scholar]
  10. Choisy M., Woelk C. H., Guégan J.-F., Robertson D. L. 2004; Comparative study of adaptive molecular evolution in different human immunodeficiency virus groups and subtypes. J Virol 78:1962–1970 [CrossRef]
     [Google Scholar]
  11. Curran R., Jameson C. L., Craggs J. K., Grabowska A. M., Thomson B. J., Robins A., Irving W. L., Ball J. K. 2002; Evolutionary trends of the first hypervariable region of the hepatitis C virus E2 protein in individuals with differing liver disease severity. J Gen Virol 83:11–23
     [Google Scholar]
  12. Doytchinova I. A., Walshe V. A., Jones N. A., Gloster S. E., Borrow P., Flower D. R. 2004; Coupling in silico and in vitro analysis of peptide-MHC binding: a bioinformatic approach enabling prediction of superbinding peptides and anchorless epitopes. J Immunol 172:7495–7502 [CrossRef]
     [Google Scholar]
  13. Farci P., Alter H. J., Wong D. C., Miller R. H., Govindarajan S., Engle R., Shapiro M., Purcell R. H. 1994; Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc Natl Acad Sci U S A 91:7792–7796 [CrossRef]
     [Google Scholar]
  14. Farci P., Shimoda A., Wong D. 7 other authors 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 [CrossRef]
     [Google Scholar]
  15. Farci P., Shimoda A., Coiana A. 9 other authors 2000; The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288:339–344 [CrossRef]
     [Google Scholar]
  16. Felsenstein J. 1985; Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791 [CrossRef]
     [Google Scholar]
  17. Flint M., Maidens C., Loomis-Price L. D., Shotton C., Dubuisson J., Monk P., Higginbottom A., Levy S., McKeating J. A. 1999; Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J Virol 73:6235–6244
     [Google Scholar]
  18. Fournillier A., Wychowski C., Boucreux D., Baumert T. F., Meunier J.-C., Jacobs D., Muguet S., Depla E., Inchauspé G. 2001; Induction of hepatitis C virus E1 envelope protein-specific immune response can be enhanced by mutation of N-glycosylation sites. J Virol 75:12088–12097 [CrossRef]
     [Google Scholar]
  19. Frasca L., Del Porto P., Tuosto L., Marinari B., Scottà C., Carbonari M., Nicosia A., Piccolella E. 1999; Hypervariable region 1 variants act as TCR antagonists for hepatitis C virus-specific CD4+ T cells. J Immunol 163:650–658
     [Google Scholar]
  20. Fukumoto T., Berg T., Ku Y., Bechstein W. O., Knoop M., Lemmens H., Lobeck H., Hopf U., Neuhaus P. 1996; Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions. Hepatology 24:1351–1354 [CrossRef]
     [Google Scholar]
  21. Garry R. F., Dash S. 2003; Proteomics computational analyses suggest that hepatitis C virus E1 and pestivirus E2 envelope glycoproteins are truncated class II fusion proteins. Virology 307:255–265 [CrossRef]
     [Google Scholar]
  22. Goffard A., Dubuisson J. 2003; Glycosylation of hepatitis C virus envelope proteins. Biochimie 85:295–301 [CrossRef]
     [Google Scholar]
  23. Gordon S. C., Elloway R. S., Long J. C., Dmuchowski C. F. 1993; The pathology of hepatitis C as a function of mode of transmission: blood transfusion vs. intravenous drug use. Hepatology 18:1338–1343 [CrossRef]
     [Google Scholar]
  24. Goulder P. J. R., Watkins D. I. 2004; HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol 4:630–640 [CrossRef]
     [Google Scholar]
  25. Gretch D. R., Polyak S. J., Wilson J. J., Carithers R. L. Jr, Perkins J. D., Corey L. 1996; Tracking hepatitis C virus quasispecies major and minor variants in symptomatic and asymptomatic liver transplant recipients. J Virol 70:7622–7631
     [Google Scholar]
  26. Grüner N. H., Gerlach T. J., Jung M.-C. 9 other authors 2000; Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C. J Infect Dis 181:1528–1536 [CrossRef]
     [Google Scholar]
  27. Honda M., Kaneko S., Sakai A., Unoura M., Murakami S., Kobayashi K. 1994; Degree of diversity of hepatitis C virus quasispecies and progression of liver disease. Hepatology 20:1144–1151 [CrossRef]
     [Google Scholar]
  28. Hsu M., Zhang J., Flint M., Logvinoff C., Cheng-Mayer C., Rice C. M., McKeating J. A. 2003; Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci U S A 100:7271–7276 [CrossRef]
     [Google Scholar]
  29. Huang X., Barchi J. J. Jr, Lung F.-D. T., Roller P. P., Nara P. L., Muschik J., Garrity R. R. 1997; Glycosylation affects both the three-dimensional structure and antibody binding properties of the HIV-1IIIB GP120 peptide RP135. Biochemistry 36:10846–10856 [CrossRef]
     [Google Scholar]
  30. Isaguliants M. G., Ozeretskovskaya N. N. 2003; Host background factors contributing to hepatitis C virus clearance. Curr Pharm Biotechnol 4:185–193 [CrossRef]
     [Google Scholar]
  31. Ishak K., Baptista A., Bianchi L. 13 other authors 1995; Histological grading and staging of chronic hepatitis. J Hepatol 22:696–699 [CrossRef]
     [Google Scholar]
  32. Jenkins G. M., Rambaut A., Pybus O. G., Holmes E. C. 2002; Rates of molecular evolution in RNA viruses: a quantitative phylogenetic analysis. J Mol Evol 54:156–165 [CrossRef]
     [Google Scholar]
  33. Kimura M. 1980; A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120 [CrossRef]
     [Google Scholar]
  34. Knodell R. G., Ishak K. G., Black W. C., Chen T. S., Craig R., Kaplowitz N., Kiernan T. W., Wollman J. 1981; Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435 [CrossRef]
     [Google Scholar]
  35. Kumar U., Monjardino J., Thomas H. C. 1994; Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient. Gastroenterology 106:1072–1075
     [Google Scholar]
  36. Kumar S., Tamura K., Jakobsen I. B., Nei M. 2001; mega2: molecular evolutionary genetic analysis software. Bioinformatics 17:1244–1245 [CrossRef]
     [Google Scholar]
  37. Lau J. Y., Davis G. L., Kniffen J., Qian K. P., Urdea M. S., Chan C. S., Mizokami M., Neuwald P. D., Wilber J. C. 1993; Significance of serum hepatitis C virus RNA levels in chronic hepatitis C. Lancet 341:1501–1504 [CrossRef]
     [Google Scholar]
  38. Li Y., Luo L., Rasool N., Kang C. Y. 1993; Glycosylation is necessary for the correct folding of human immunodeficiency virus gp120 in CD4 binding. J Virol 67:584–588
     [Google Scholar]
  39. Lindenbach B. D., Rice C. M. 2001; Flaviviridae : the viruses and their replication. In Fields Virology , 4th edn. pp  991–1041 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
     [Google Scholar]
  40. Majid A., Jackson P., Lawal Z., Pearson G. M. J., Parker H., Alexander G. J. M., Allain J.-P., Petrik J. 1999; Ontogeny of hepatitis C virus (HCV) hypervariable region 1 (HVR1) heterogeneity and HVR1 antibody responses over a 3 year period in a patient infected with HCV type 2b. J Gen Virol 80:317–325
     [Google Scholar]
  41. Marrone A., Sallie R. 1996; Genetic heterogeneity of hepatitis C virus. The clinical significance of genotypes and quasispecies behavior. Clin Lab Med 16:429–449
     [Google Scholar]
  42. Martell M., Esteban J. I., Quer J., Genescà J., Weiner A., Esteban R., Guardia J., Gómez J. 1992; Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol 66:3225–3229
     [Google Scholar]
  43. Martin P., Di Bisceglie A. M., Kassianides C., Lisker-Melman M., Hoofnagle J. H. 1989; Rapidly progressive non-A, non-B hepatitis in patients with human immunodeficiency virus infection. Gastroenterology 97:1559–1561
     [Google Scholar]
  44. McAllister J., Casino C., Davidson F., Power J., Lawlor E., Peng L. Y., Simmonds P., Smith D. B. 1998; Long-term evolution of the hypervariable region of hepatitis C virus in a common-source-infected cohort. J Virol 72:4893–4905
     [Google Scholar]
  45. McCormack G. P., Clewley J. P. 2002; The application of molecular phylogenetics to the analysis of viral genome diversity and evolution. Rev Med Virol 12:221–238 [CrossRef]
     [Google Scholar]
  46. Meunier J.-C., Fournillier A., Choukhi A., Cahour A., Cocquerel L., Dubuisson J., Wychowski C. 1999; Analysis of the glycosylation sites of hepatitis C virus (HCV) glycoprotein E1 and the influence of E1 glycans on the formation of the HCV glycoprotein complex. J Gen Virol 80:887–896
     [Google Scholar]
  47. 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 [CrossRef]
     [Google Scholar]
  48. Mohsen A. H. 2001; The epidemiology of hepatitis C in a UK health regional population of 5·12 million. Gut 48:707–713 [CrossRef]
     [Google Scholar]
  49. Muller R. 1996; The natural history of hepatitis C: clinical experiences. J Hepatol 24:52–54 [CrossRef]
     [Google Scholar]
  50. Neumann A. U., Lam N. P., Dahari H., Gretch D. R., Wiley T. E., Layden T. J., Perelson A. S. 1998; Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon- α therapy. Science 282:103–107 [CrossRef]
     [Google Scholar]
  51. Okamoto H., Kojima M., Okada S. I. 7 other authors 1992; Genetic drift of hepatitis C virus during an 8·2-year infection in a chimpanzee: variability and stability. Virology 190:894–899 [CrossRef]
     [Google Scholar]
  52. Owsianka A., Clayton R. F., Loomis-Price L. D., McKeating J. A., Patel A. H. 2001; Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2. J Gen Virol 82:1877–1883
     [Google Scholar]
  53. Parker K. C., Bednarek M. A., Coligan J. E. 1994; Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 152:163–175
     [Google Scholar]
  54. 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 [CrossRef]
     [Google Scholar]
  55. Pinter A., Honnen W. J., He Y., Gorny M. K., Zolla-Pazner S., Kayman S. C. 2004; The V1/V2 domain of gp120 is a global regulator of the sensitivity of primary human immunodeficiency virus type 1 isolates to neutralization by antibodies commonly induced upon infection. J Virol 78:5205–5215 [CrossRef]
     [Google Scholar]
  56. Pugach P., Kuhmann S. E., Taylor J., Marozsan A. J., Snyder A., Ketas T., Wolinsky S. M., Korber B. T., Moore J. P. 2004; The prolonged culture of human immunodeficiency virus type 1 in primary lymphocytes increases its sensitivity to neutralization by soluble CD4. Virology 321:8–22 [CrossRef]
     [Google Scholar]
  57. Puntoriero G., Meola A., Lahm A. 9 other authors 1998; Towards a solution for hepatitis C virus hypervariability: mimotopes of the hypervariable region 1 can induce antibodies cross-reacting with a large number of viral variants. EMBO J 17:3521–3533 [CrossRef]
     [Google Scholar]
  58. Rambaut A. 2000; Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies. Bioinformatics 16:395–399 [CrossRef]
     [Google Scholar]
  59. Ramratnam B., Bonhoeffer S., Binley J. 7 other authors 1999; Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 354:1782–1785 [CrossRef]
     [Google Scholar]
  60. Ray S. C., Wang Y.-M., Laeyendecker O., Ticehurst J. R., Villano S. A., Thomas D. L. 1999; Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy. J Virol 73:2938–2946
     [Google Scholar]
  61. Robertson D. L., Hahn B. H., Sharp P. M. 1995; Recombination in AIDS viruses. J Mol Evol 40:249–259 [CrossRef]
     [Google Scholar]
  62. Roccasecca R., Ansuini H., Vitelli A. 11 other authors 2003; Binding of the hepatitis C virus E2 glycoprotein to CD81 is strain specific and is modulated by a complex interplay between hypervariable regions 1 and 2. J Virol 77:1856–1867 [CrossRef]
     [Google Scholar]
  63. Rosa D., Campagnoli S., Moretto C. 11 other authors 1996; A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc Natl Acad Sci U S A 93:1759–1763 [CrossRef]
     [Google Scholar]
  64. Ryder S. D., Irving W. L., Jones D. A., Neal K. R., Underwood J. C. 2004; Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study. Gut 53:451–455 [CrossRef]
     [Google Scholar]
  65. Saito I., Miyamura T., Ohbayashi A. 10 other authors 1990; Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A 87:6547–6549 [CrossRef]
     [Google Scholar]
  66. Saitou N., Nei M. 1987; The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425
     [Google Scholar]
  67. Scarselli E., Ansuini H., Cerino R. 7 other authors 2002; The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21:5017–5025 [CrossRef]
     [Google Scholar]
  68. Schønning K., Jansson B., Olofsson S., Hansen J.-E. S. 1996; Rapid selection for an N -linked oligosaccharide by monoclonal antibodies directed against the V3 loop of human immunodeficiency virus type 1. J Gen Virol 77:753–758 [CrossRef]
     [Google Scholar]
  69. Serra M. A., Rodríguez F., del Olmo J. A., Escudero A., Rodrigo J. M. 2003; Influence of age and date of infection on distribution of hepatitis C virus genotypes and fibrosis stage. J Viral Hepat 10:183–188 [CrossRef]
     [Google Scholar]
  70. Sheridan I., Pybus O. G., Holmes E. C., Klenerman P. 2004; High-resolution phylogenetic analysis of hepatitis C virus adaptation and its relationship to disease progression. J Virol 78:3447–3454 [CrossRef]
     [Google Scholar]
  71. Shimizu Y. K., Hijikata M., Iwamoto A., Alter H. J., Purcell R. H., Yoshikura H. 1994; Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J Virol 68:1494–1500
     [Google Scholar]
  72. Shimizu Y., Igarashi H., Kiyohara T., Cabezon T., Farci P., Purcell R. H., Yoshikura H. 1996; A hyperimmune serum against a synthetic peptide corresponding to the hypervariable region 1 of hepatitis C virus can prevent viral infection in cell cultures. Virology 223:409–412 [CrossRef]
     [Google Scholar]
  73. Shirai M., Arichi T., Nishioka M., Nomura T., Ikeda K., Kawanishi K., Engelhard V. H., Feinstone S. M., Berzofsky J. A. 1995; CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1. J Immunol 154:2733–2742
     [Google Scholar]
  74. Shoukry N. H., Cawthon A. G., Walker C. M. 2004; Cell-mediated immunity and the outcome of hepatitis C virus infection. Annu Rev Microbiol 58:391–424 [CrossRef]
     [Google Scholar]
  75. Smith D. B. 1999; Evolution of the hypervariable region of hepatitis C virus. J Viral Hepat 6:41–46 [CrossRef]
     [Google Scholar]
  76. Sullivan J., Swofford D. L., Naylor G. J. P. 1999; The effect of taxon sampling on estimating rate heterogeneity parameters of maximum-likelihood models. Mol Biol Evol 16:1347–1356 [CrossRef]
     [Google Scholar]
  77. Swofford D. L. 2003 paup*: Phylogenetic Analysis Using Parsinomy (*and other methods), version 4 Sunderland. MA: Sinauer Associates;
     [Google Scholar]
  78. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. 1997; The clustal_x windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882 [CrossRef]
     [Google Scholar]
  79. Tsai S. L., Chen Y. M., Chen M. H., Huang C. Y., Sheen I. S., Yeh C. T., Huang J. H., Kuo G. C., Liaw Y. F. 1998; Hepatitis C virus variants circumventing cytotoxic T lymphocyte activity as a mechanism of chronicity. Gastroenterology 115:954–965 [CrossRef]
     [Google Scholar]
  80. Urbani S., Uggeri J., Matsuura Y., Miyamura T., Penna A., Boni C., Ferrari C. 2001; Identification of immunodominant hepatitis C virus (HCV)-specific cytotoxic T-cell epitopes by stimulation with endogenously synthesized HCV antigens. Hepatology 33:1533–1543 [CrossRef]
     [Google Scholar]
  81. Wack A., Soldaini E., Tseng C.-T. K., Nuti S., Klimpel G. R., Abrignani S. 2001; Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells. Eur J Immunol 31:166–175 [CrossRef]
     [Google Scholar]
  82. Wang H., Eckels D. D. 1999; Mutations in immunodominant T cell epitopes derived from the nonstructural 3 protein of hepatitis C virus have the potential for generating escape variants that may have important consequences for T cell recognition. J Immunol 162:4177–4183
     [Google Scholar]
  83. Ward S., Lauer G., Isba R., Walker B., Klenerman P. 2002; Cellular immune responses against hepatitis C virus: the evidence base 2002. Clin Exp Immunol 128:195–203 [CrossRef]
     [Google Scholar]
  84. Wei X., Decker J. M., Wang S. 12 other authors 2003; Antibody neutralization and escape by HIV-1. Nature 422:307–312 [CrossRef]
     [Google Scholar]
  85. Weltman M. D., Brotodihardjo A., Crewe E. B., Farrell G. C., Bilous M., Grierson J. M., Liddle C. 1995; Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment. J Viral Hepat 2:39–45 [CrossRef]
     [Google Scholar]
  86. WHO 1999; Global surveillance and control of hepatitis C. J Viral Hepat 6:35–47 [CrossRef]
     [Google Scholar]
  87. Wu Z., Kayman S. C., Honnen W. 7 other authors 1995; Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. J Virol 69:2271–2278
     [Google Scholar]
  88. Yagnik A. T., Lahm A., Meola A., Roccasecca R. M., Ercole B. B., Nicosia A., Tramontano A. 2000; A model for the hepatitis C virus envelope glycoprotein E2. Proteins 40:355–366 [CrossRef]
     [Google Scholar]
  89. Yang Z. 1994a; Estimating the pattern of nucleotide substitution. J Mol Evol 39:105–111
     [Google Scholar]
  90. Yang Z. 1994b; Maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: approximate methods. J Mol Evol 39:306–314 [CrossRef]
     [Google Scholar]
  91. Yang Z. 1997; paml: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 13:555–556
     [Google Scholar]
  92. Yang Z., Bielawski J. P. 2000; Statistical methods for detecting molecular adaptation. Trends Ecol Evol 15:496–503 [CrossRef]
     [Google Scholar]
  93. Yu K., Petrovsky N., Schonbach C., Koh J. Y., Brusic V. 2002; Methods for prediction of peptide binding to MHC molecules: a comparative study. Mol Med 8:137–148
     [Google Scholar]
  94. Zaphiropoulos P. G. 2002; Template switching generated during reverse transcription?. FEBS Lett 527:326 [CrossRef]
     [Google Scholar]
  95. Zeuzem S. 2000; Hepatitis C virus: kinetics and quasispecies evolution during anti-viral therapy. Forum 10:32–42
     [Google Scholar]
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Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection
J. Gen. Virol. 86, 1931 (2005); https://doi.org/10.1099/vir.0.80957-0
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