1887

Abstract

To date, all studies regarding hepatitis C virus (HCV) F protein have been based on expression of recombinant protein or monoclonal antibodies derived from genotype 1a or 1b sequences, but not from other genotypes. The objective of this study was to prepare a putative genotype 2 recombinant F protein and evaluate its reactivity in plasma from individuals with chronic HCV infection or who had recovered from infection. One genotype 2 strain was selected for F protein (F-2) and core expression in bacterial culture. An ELISA was developed and applied to samples from patients with chronic infection or recovered infection of various genotypes. The anti-F-2 response in 117 samples showed a significantly higher reactivity in chronic than in recovered HCV-infected blood donors (<0.001), but no difference was found among genotypes. However, the correlation between anti-F and anti-core was more significant in genotypes 1 and 2 than in genotype 3. Anti-F-2 titres were also significantly higher in chronic than in recovered individuals (<0.0001). Antibody titres to recombinant genotype 2 core protein or to genotype 1 multiple proteins used in commercial anti-HCV assays paralleled the anti-F-2 end-point antibody titre. This study thus demonstrated the antigenicity of genotype 2 HCV F protein, although the exact location of the natural frameshift position remains unknown. The difference in anti-F-2 response between chronic and recovered infection, the cross-reactivity irrespective of genotype and the correlation of antibody response with structural and non-structural antigens suggest that the immune response to F protein is an integral part of the natural HCV infection.

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2008-08-01
2024-12-08
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References

  1. Bain C., Parroche P., Lavergne J. P., Duverger B., Vieux C., Dubois V., Komurian-Pradel F., Trepo C., Gebuhrer L. other authors 2004; Memory T-cell-mediated immune responses specific to an alternative core protein in hepatitis C virus infection. J Virol 78:10460–10469 [CrossRef]
    [Google Scholar]
  2. Baril M., Brakier-Gingras L. 2005; Translation of the F protein of hepatitis C virus is initiated at a non-AUG codon in a +1 reading frame relative to the polyprotein. Nucleic Acids Res 33:1474–1486 [CrossRef]
    [Google Scholar]
  3. Basu A., Steele R., Ray R., Ray R. B. 2004; Functional properties of a 16 kDa protein translated from an alternative open reading frame of the core-encoding genomic region of hepatitis C virus. J Gen Virol 85:2299–2306 [CrossRef]
    [Google Scholar]
  4. Boulant S., Becchi M., Penin F., Lavergne J. P. 2003; Unusual multiple recoding events leading to alternative forms of hepatitis C virus core protein from genotype 1b. J Biol Chem 278:45785–45792 [CrossRef]
    [Google Scholar]
  5. Choi J., Xu Z., Ou J. H. 2003; Triple decoding of hepatitis C virus RNA by programmed translational frameshifting. Mol Cell Biol 23:1489–1497 [CrossRef]
    [Google Scholar]
  6. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. 1989; Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362 [CrossRef]
    [Google Scholar]
  7. Chuang W. C., Sarkodie F., Brown C. J., Owusu-Ofori S., Brown J., Li C., Navarrete C., Klenerman P., Allain J. P. 2007; Protective effect of HLA-B57 on HCV genotype 2 infection in a West African population. J Med Virol 79:724–733 [CrossRef]
    [Google Scholar]
  8. Cohen M., Bachmatov L., Ben-Ari Z., Rotman Y., Tur-Kaspa R., Zemel R. 2007; Development of specific antibodies to an ARF protein in treated patients with chronic HCV infection. Dig Dis Sci 52:2427–2432 [CrossRef]
    [Google Scholar]
  9. Cristina J., Lopez F., Moratorio G., Lopez L., Vasquez S., Garcia-Aguirre L., Chunga A. 2005; Hepatitis C virus F protein sequence reveals a lack of functional constraints and a variable pattern of amino acid substitution. J Gen Virol 86:115–120 [CrossRef]
    [Google Scholar]
  10. Dhaliwal S. K., Prescott L. E., Dow B. C., Davidson F., Brown H., Yap P. L., Follett E. A., Simmonds P. 1996; Influence of viraemia and genotype upon serological reactivity in screening assays for antibody to hepatitis C virus. J Med Virol 48:184–190 [CrossRef]
    [Google Scholar]
  11. Fiorucci M., Boulant S., Fournillier A., Abraham J. D., Lavergne J. P., Paranhos-Baccala G., Inchauspe G., Bain C. 2007; Expression of the alternative reading frame protein of Hepatitis C virus induces cytokines involved in hepatic injuries. J Gen Virol 88:1149–1162 [CrossRef]
    [Google Scholar]
  12. Jackson P., Petrik J., Alexander G. J., Pearson G., Allain J. P. 1997; Reactivity of synthetic peptides representing selected sections of hepatitis C virus core and envelope proteins with a panel of hepatitis C virus-seropositive human plasma. J Med Virol 51:67–79 [CrossRef]
    [Google Scholar]
  13. Kaito M., Watanabe S., Tsukiyama-Kohara K., Yamaguchi K., Kobayashi Y., Konishi M., Yokoi M., Ishida S., Suzuki S., Kohara M. 1994; Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol 75:1755–1760 [CrossRef]
    [Google Scholar]
  14. Komurian-Pradel F., Rajoharison A., Berland J. L., Khouri V., Perret M., Van Roosmalen M., Pol S., Negro F., Paranhos-Baccala G. 2004; Antigenic relevance of F protein in chronic hepatitis C virus infection. Hepatology 40:900–909 [CrossRef]
    [Google Scholar]
  15. Lo S. Y., Selby M., Tong M., Ou J. H. 1994; Comparative studies of the core gene products of two different hepatitis C virus isolates: two alternative forms determined by a single amino acid substitution. Virology 199:124–131 [CrossRef]
    [Google Scholar]
  16. Nikolaeva L. I., Blokhina N. P., Tsurikova N. N., Voronkova N. V., Miminoshvili M. I., Braginsky D. M., Yastrebova O. N., Booynitskaya O. B., Isaeva O. V. other authors 2002; Virus-specific antibody titres in different phases of hepatitis C virus infection. J Viral Hepat 9:429–437 [CrossRef]
    [Google Scholar]
  17. Ogata S., Nagano-Fujii M., Ku Y., Yoon S., Hotta H. 2002; Comparative sequence analysis of the core protein and its frameshift product, the F protein, of hepatitis C virus subtype 1b strains obtained from patients with and without hepatocellular carcinoma. J Clin Microbiol 40:3625–3630 [CrossRef]
    [Google Scholar]
  18. Park Y. M., Byun B. H., Choi J. Y., Bae S. H., Kim B. S., So H. S., Ryu W. S. 1999; Monitoring antibody titers to recombinant Core–NS3 fusion polypeptide is useful for evaluating hepatitis C virus infection and responses to interferon-alpha therapy. J Korean Med Sci 14:165–170 [CrossRef]
    [Google Scholar]
  19. Pereboeva L. A., Pereboev A. V., Morris G. E. 1998; Identification of antigenic sites on three hepatitis C virus proteins using phage-displayed peptide libraries. J Med Virol 56:105–111 [CrossRef]
    [Google Scholar]
  20. Roussel J., Pillez A., Montpellier C., Duverlie G., Cahour A., Dubuisson J., Wychowski C. 2003; Characterization of the expression of the hepatitis C virus F protein. J Gen Virol 84:1751–1759 [CrossRef]
    [Google Scholar]
  21. Simmonds P., Bukh J., Combet C., Deleage G., Enomoto N., Feinstone S., Halfon P., Inchauspe 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]
  22. Trestard A., Bacq Y., Buzelay L., Dubois F., Barin F., Goudeau A., Roingeard P. 1998; Ultrastructural and physicochemical characterization of the hepatitis C virus recovered from the serum of an agammaglobulinemic patient. Arch Virol 143:2241–2245 [CrossRef]
    [Google Scholar]
  23. Troesch M., Jalbert E., Canobio S., Boulassel M. R., Routy J. P., Bernard N. F., Bruneau J., Lapointe N., Boucher M., Soudeyns H. 2005; Characterization of humoral and cell-mediated immune responses directed against hepatitis C virus F protein in subjects co-infected with hepatitis C virus and HIV-1. AIDS 19:775–784 [CrossRef]
    [Google Scholar]
  24. Tsao M. L., Chao C. H., Yeh C. T. 2006; Interaction of hepatitis C virus F protein with prefoldin 2 perturbs tubulin cytoskeleton organization. Biochem Biophys Res Commun 348:271–277 [CrossRef]
    [Google Scholar]
  25. Varaklioti A., Vassilaki N., Georgopoulou U., Mavromara P. 2002; Alternate translation occurs within the core coding region of the hepatitis C viral genome. J Biol Chem 277:17713–17721 [CrossRef]
    [Google Scholar]
  26. Vassilaki N., Mavromara P. 2003; Two alternative translation mechanisms are responsible for the expression of the HCV ARFP/F/core+1 coding open reading frame. J Biol Chem 278:40503–40513 [CrossRef]
    [Google Scholar]
  27. Walewski J. L., Keller T. R., Stump D. D., Branch A. D. 2001; Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame. RNA 7:710–721 [CrossRef]
    [Google Scholar]
  28. Xu Z., Choi J., Yen T. S., Lu W., Strohecker A., Govindarajan S., Chien D., Selby M. J., Ou J. 2001; Synthesis of a novel hepatitis C virus protein by ribosomal frameshift. EMBO J 20:3840–3848 [CrossRef]
    [Google Scholar]
  29. Xu Z., Choi J., Lu W., Ou J. H. 2003; Hepatitis C virus F protein is a short-lived protein associated with the endoplasmic reticulum. J Virol 77:1578–1583 [CrossRef]
    [Google Scholar]
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