1887

Abstract

Hepatitis C virus (HCV) encodes two glycoproteins, E1 and E2, which assemble in oligomeric structures. Studies of HCV glycoprotein assembly using heterologous expression systems have shown that these glycoproteins can follow two pathways: a productive pathway leading to the formation of a non-covalent heterodimer; and a non-productive pathway leading to the formation of large disulfide-linked aggregates. The non-covalent HCV glycoprotein complex is probably the functional complex which plays an active role in the entry process in host cells. The aggregates are believed to be waste products; however, one can imagine that, in infected cells, they could provide HCV glycoproteins with additional functions. To further understand the potential role played by HCV glycoprotein aggregates in HCV infection, a MAb (H14) was produced which specifically recognizes these aggregates but not the non-covalent E1E2 heterodimer. The H14 epitope was shown to be present on both HCV glycoproteins and was sensitive to deglycosylation. An additional characterization of HCV glycoprotein aggregates, with the help of MAb H14, indicates that they share an epitope with a cellular protein called Mac-2 binding protein. The presence of such an epitope on HCV glycoprotein aggregates could potentially lead to the production of autoantibodies recognizing Mac-2 binding protein in HCV-infected patients.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-12-3099
1999-12-01
2019-10-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/12/0803099.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-12-3099&mimeType=html&fmt=ahah

References

  1. Chamberlain, J. P. ( 1979; ). Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Analytical Biochemistry 98, 132-135.[CrossRef]
    [Google Scholar]
  2. Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O’Riordan, C. R. & Smith, A. E. ( 1990; ). Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63, 827-834.[CrossRef]
    [Google Scholar]
  3. Choukhi, A., Ung, S., Wychowski, C. & Dubuisson, J. ( 1998; ). Involvement of endoplasmic reticulum chaperones in folding of hepatitis C virus glycoproteins. Journal of Virology 72, 3851-3858.
    [Google Scholar]
  4. Cocquerel, L., Meunier, J.-C., Pillez, A., Wychowski, C. & Dubuisson, J. ( 1998; ). A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2. Journal of Virology 72, 2183-2191.
    [Google Scholar]
  5. Cocquerel, L., Duvet, S., Meunier, J.-C., Pillez, A., Cacan, R., Wychowski, C. & Dubuisson, J. ( 1999; ). The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum. Journal of Virology 73, 2641-2649.
    [Google Scholar]
  6. Deleersnyder, V., Pillez, A., Wychowski, C., Blight, K., Xu, J., Hahn, Y. S., Rice, C. M. & Dubuisson, J. ( 1997; ). Formation of native hepatitis C virus glycoprotein complexes. Journal of Virology 71, 697-704.
    [Google Scholar]
  7. Denning, G. M., Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E. & Welsh, M. J. ( 1992; ). Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature 358, 761-764.[CrossRef]
    [Google Scholar]
  8. Dobson, C. M. & Ellis, R. J. ( 1998; ). Protein folding and misfolding inside and outside the cell. EMBO Journal 17, 5251-5254.[CrossRef]
    [Google Scholar]
  9. Dubuisson, J. ( 1999; ). Folding, assembly and subcellular localization of HCV glycoproteins. Current Topics in Microbiology and Immunology 242, 135-148.
    [Google Scholar]
  10. Dubuisson, J. & Rice, C. M. ( 1996; ). Hepatitis C virus glycoprotein folding: disulfide bond formation and association with calnexin. Journal of Virology 70, 778-786.
    [Google Scholar]
  11. Dubuisson, J., Hsu, H. H., Cheung, R. C., Greenberg, H. B., Russell, D. G. & Rice, C. M. ( 1994; ). Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses. Journal of Virology 68, 6147-6160.
    [Google Scholar]
  12. Durrazzo, M., Philipp, T., Van Pelt, F. N., Luttig, B., Borghesio, E., Michel, G., Schmidt, E., Loges, S., Rizzetto, M. & Manns, M. P. ( 1995; ). Heterogeneity of microsomal autoantibodies (LKM) in chronic hepatitis C and D virus infection. Gastroenterology 108, 455-462.[CrossRef]
    [Google Scholar]
  13. Duvet, S., Cocquerel, L., Pillez, A., Cacan, R., Verbert, A., Moradpour, D., Wychowski, C. & Dubuisson, J. ( 1998; ). Hepatitis C virus glycoprotein complex localization in the endoplasmic reticulum involves a determinant for retention and not retrieval. Journal of Biological Chemistry 273, 32088-32095.[CrossRef]
    [Google Scholar]
  14. Fischer, G. & Schmid, F. X. ( 1990; ). The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell. Biochemistry 29, 2205-2212.[CrossRef]
    [Google Scholar]
  15. Fournillier-Jacob, A., Cahour, A., Escriou, N., Girard, M. & Wychowski, C. ( 1996; ). Processing of the E1 glycoprotein of hepatitis C virus expressed in mammalian cells. Journal of General Virology 77, 1055-1064.[CrossRef]
    [Google Scholar]
  16. Fuerst, T. R., Niles, E. G., Studier, F. W. & Moss, B. ( 1986; ). Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proceedings of the National Academy of Sciences, USA 83, 8122-8126.[CrossRef]
    [Google Scholar]
  17. Grakoui, A., Wychowski, C., Lin, C., Feinstone, S. M. & Rice, C. M. ( 1993; ). Expression and identification of hepatitis C virus polyprotein cleavage products. Journal of Virology 67, 1385-1395.
    [Google Scholar]
  18. Habersetzer, F., Fournillier, A., Dubuisson, J., Rosa, D., Abrigniani, S., Wychowski, C., Nakano, I., Trépo, C., Desgranges, C. & Inchauspé, G. ( 1998; ). Characterization of human monoclonal antibodies specific of the hepatitis C virus glycoprotein E2 with in vitro binding neutralization properties. Virology 249, 32-41.[CrossRef]
    [Google Scholar]
  19. Harlow, E. & Lane, D. P. (1988). Antibodies: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  20. Houghton, M. ( 1996; ). Hepatitis C viruses. In Fields Virology, pp. 1035-1058. Edited by B. N. Fields, D. M. Knipe & P. M. Howley. Philadelphia: Lippincott–Raven.
  21. Kolykhalov, A. A., Agapov, E. V., Blight, K., Mihalik, K., Feinstone, S. M. & Rice, C. M. ( 1997; ). Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277, 570-574.[CrossRef]
    [Google Scholar]
  22. Koths, K., Taylor, E., Halenbeck, R., Casipit, C. & Wang, A. ( 1993; ). Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain. Journal of Biological Chemistry 268, 14245-14249.
    [Google Scholar]
  23. Laemmli, U. K. ( 1970; ). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.[CrossRef]
    [Google Scholar]
  24. Lanford, R. E., Notvall, L., Chavez, D., White, R., Frenzel, G., Simonsen, C. & Kim, J. ( 1993; ). Analysis of hepatitis C virus capsid, E1, and E2/NS1 proteins expressed in insect cells. Virology 197, 225-235.[CrossRef]
    [Google Scholar]
  25. Manns, M. P. & Obermayer-Straub, P. ( 1997; ). Viral induction of autoimmunity: mechanisms and examples in hepatology. Journal of Viral Hepatitis 4 (suppl. 2), 42–47.
    [Google Scholar]
  26. Michalak, J.-P., Wychowski, C., Choukhi, A., Meunier, J.-C., Ung, S., Rice, C. M. & Dubuisson, J. ( 1997; ). Characterization of truncated forms of hepatitis C virus glycoproteins. Journal of General Virology 78, 2299-2306.
    [Google Scholar]
  27. Ralston, R., Thudium, K., Berger, K., Kuo, C., Gervase, B., Hall, J., Selby, M., Kuo, G., Houghton, M. & Choo, Q.-L. ( 1993; ). Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses. Journal of Virology 67, 6753-6761.
    [Google Scholar]
  28. Rosenfeld, J., Capdeville, J., Guillemot, J. & Ferrara, P. ( 1992; ). In-gel digestion of proteins for internal sequence analysis after 1 or 2 dimensional gel electrophoresis. Analytical Biochemistry 203, 173-179.[CrossRef]
    [Google Scholar]
  29. Sasaki, T., Brakebusch, C., Engel, J. & Timpl, R. ( 1998; ). Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds β1 integrins, collagens and fibronectin. EMBO Journal 17, 1606-1613.[CrossRef]
    [Google Scholar]
  30. Thomas, P. J., Shebagamurthi, P., Sondek, J., Hullihen, J. M. & Pedersen, P. L. ( 1992; ). The cystic fibrosis transmembrane conductance regulator. Effects of most common cystic fibrosis-causing mutation on the secondary structure and stability of a synthetic peptide. Journal of Biological Chemistry 267, 5727-5730.
    [Google Scholar]
  31. Thomas, P. J., Qu, B.-H. & Pedersen, P. L. ( 1995; ). Defective protein folding as a basis of human disease. Trends in Biochemical Sciences 20, 456-459.[CrossRef]
    [Google Scholar]
  32. Ulrich, A., Sures, I., D’Egidio, M., Jallal, B., Powell, T. J., Herbst, R., Dreps, A., Azam, M., Rubinstein, M., Natoli, C., Shawver, L. K., Schlessinger, J. & Iacobelli, S. ( 1994; ). The secreted tumor-associated antigen 90K is a potent immune stimulator. Journal of Biological Chemistry 269, 18401-18407.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-12-3099
Loading
/content/journal/jgv/10.1099/0022-1317-80-12-3099
Loading

Data & Media loading...

Most Cited This Month

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