1887

Abstract

A replication-defective herpes simplex virus type 1 (HSV-1) recombinant lacking the glycoprotein H (gH)-encoding gene and expressing a truncated form of the hepatitis C (HCV) E2 glycoprotein (E2-661) was constructed and characterized. We show here that cells infected with the HSV/HCV recombinant virus efficiently express the HCV E2-661 protein. Most importantly, cellular and secreted E2-661 protein were both readily detected by the E2-conformational mAb H53 and despite the high expression levels, only limited amounts of misfolded aggregates were detected in either the cellular or secreted fractions. Furthermore, cell-associated and secreted E2-661 protein bound to the major extracellular loop (MEL) of CD81 in a concentration-dependent manner and both were highly reactive with sera from HCV-infected patients. Finally, BALB/c mice immunized intraperitoneally with the recombinant HSV/HCV virus induced high levels of anti-E2 antibodies. Analysis of the induced immunoglobulin G (IgG) isotypes showed high levels of IgG2a while the levels of the IgG1 isotype were significantly lower, suggesting a Th1-type of response. We conclude that the HSV-1 recombinant virus represents a promising tool for production of non-aggregated, immunologically active forms of the E2-661 protein and might have potential applications in vaccine development.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.18775-0
2003-03-01
2020-08-11
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/3/vir840545.html?itemId=/content/journal/jgv/10.1099/vir.0.18775-0&mimeType=html&fmt=ahah

References

  1. Abrignani S., Rosa D.. 1998; Perspectives for a hepatitis C virus vaccine. Clin Diagn Virol10:181–185
    [Google Scholar]
  2. Brockman M. A., Knipe D. M.. 2002; Herpes simplex virus vectors elicit durable immune responses in the presence of preexisting host immunity. J Virol76:3678–3687
    [Google Scholar]
  3. Buonocore L., Blight K. J., Rice C. M., Rose J. K.. 2002; Characterization of vesicular stomatitis virus recombinants that express and incorporate high levels of hepatitis C virus glycoproteins. J Virol76:6865–6872
    [Google Scholar]
  4. Chien D. Y., Choo Q. L., Tabrizi A.. 16 other authors 1992; Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. Proc Natl Acad Sci U S A89:10011–10015
    [Google Scholar]
  5. Chien D. Y., Choo Q. L., Ralston R., Spaete R., Tong M., Houghton M., Kuo G.. 1993; Persistence of HCV despite antibodies to both putative envelope glycoproteins. Lancet342:933
    [Google Scholar]
  6. Choo Q. L., Kuo G., Ralston R.. 15 other authors 1994; Vaccination of chimpanzees against infection by the hepatitis C virus. Proc Natl Acad Sci U S A91:1294–1298
    [Google Scholar]
  7. Choukhi A., Ung S., Wychowski C., Dubuisson J.. 1998; Involvement of endoplasmic reticulum chaperones in the folding of hepatitis C virus glycoproteins. J Virol72:3851–3858
    [Google Scholar]
  8. Choukhi A., Pillez A., Drobecq H., Sergheraert C., Wychowski C., Dubuisson J.. 1999; Characterization of aggregates of hepatitis C virus glycoproteins. J Gen Virol80:3099–3107
    [Google Scholar]
  9. 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. J Virol72:2183–2191
    [Google Scholar]
  10. Cohen J.. 1999; The scientific challenge of hepatitis C. Science285:26–30
    [Google Scholar]
  11. Da Costa X. J., Morrison L. A., Knipe D. M.. 2001; Comparison of different forms of herpes simplex replication-defective mutant viruses as vaccines in a mouse model of HSV-2 genital infection. Virology288:256–263
    [Google Scholar]
  12. 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. J Virol71:697–704
    [Google Scholar]
  13. Depraetere S., Leroux-Roels G.. 1999; Hepatitis C virus envelope proteins: immunogenicity in humans and their role in diagnosis and vaccine development. Viral Hep Rev5:113–146
    [Google Scholar]
  14. Dubuisson J.. 1998; The role of chaperone proteins in the assembly of envelope proteins of hepatitis C virus. Bull Mem Acad R Med Belg153:343–349
    [Google Scholar]
  15. 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. J Virol68:6147–6160
    [Google Scholar]
  16. 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. J Biol Chem273:32088–32095
    [Google Scholar]
  17. Flint M., Thomas J. M., Maidens C. M., Shotton C., Levy S., Barclay W. S., McKeating J. A.. 1999; Functional analysis of cell surface-expressed hepatitis C virus E2 glycoprotein. J Virol73:6782–6790
    [Google Scholar]
  18. Flint M., Dubuisson J., Maidens C., Harrop R., Guile G. R., Borrow P., McKeating J. A.. 2000; Functional characterization of intracellular and secreted forms of a truncated hepatitis C virus E2 glycoprotein. J Virol74:702–709
    [Google Scholar]
  19. Forns X., Emerson S. U., Tobin G. J., Mushahwar I. K., Purcell R. H., Bukh J.. 1999; DNA immunization of mice and macaques with plasmids encoding hepatitis C virus envelope E2 protein expressed intracellularly and on the cell surface. Vaccine17:1992–2002
    [Google Scholar]
  20. Forrester A., Farrell H., Wilkinson G., Kaye J., Davis-Poynter N., Minson T.. 1992; Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. J Virol66:341–348
    [Google Scholar]
  21. Fournillier-Jacob A., Lunel F., Cahour A., Cresta P., Frangeul L., Perrin M., Girard M., Wychowski C.. 1996; Antibody responses to hepatitis C envelope proteins in patients with acute or chronic hepatitis C. J Med Virol50:159–167
    [Google Scholar]
  22. Hoofnagle J. H.. 1997; Hepatitis C: the clinical spectrum of disease. Hepatology26:15S–20S
    [Google Scholar]
  23. Hussy P., Faust H., Wagner J. C., Schmid G., Mous J., Jacobsen H.. 1997; Evaluation of hepatitis C virus envelope proteins expressed in E. coli and insect cells for use as tools for antibody screening. J Hepatol26:1179–1186
    [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. Virology197:225–235
    [Google Scholar]
  25. Latchman D. S.. 2001; Gene delivery and gene therapy with herpes simplex virus-based vectors. Gene264:1–9
    [Google Scholar]
  26. Lauer G. M., Walker B. D.. 2001; Hepatitis C virus infection. N Engl J Med345:41–52
    [Google Scholar]
  27. Lesniewski R., Okasinski G., Carrick R., Van Sant C., Desai S., Johnson R., Scheffel J., Moore B., Mushahwar I.. 1995; Antibody to hepatitis C virus second envelope (HCV-E2) glycoprotein: a new marker of HCV infection closely associated with viremia. J Med Virol45:415–422
    [Google Scholar]
  28. Lok A. S., Chien D., Choo Q. L., Chan T. M., Chiu E. K., Cheng I. K., Houghton M., Kuo G.. 1993; Antibody response to core, envelope and nonstructural hepatitis C virus antigens: comparison of immunocompetent and immunosuppressed patients. Hepatology18:497–502
    [Google Scholar]
  29. Loudon P. T., Blakeley D. M., Boursnell M. E.. 7 other authors 2001; Preclinical safety testing of DISC-hGMCSF to support phase I clinical trials in cancer patients. J Gene Med3:458–467
    [Google Scholar]
  30. Matsuura Y., Harada S., Suzuki R., Watanabe Y., Inoue Y., Saito I., Miyamura T.. 1992; Expression of processed envelope protein of hepatitis C virus in mammalian and insect cells. J Virol66:1425–1431
    [Google Scholar]
  31. 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. J Gen Virol78:2299–2306
    [Google Scholar]
  32. Mink M. A., Benichou S., Madaule P., Tiollais P., Prince A. M., Inchauspe G.. 1994; Characterization and mapping of a B-cell immunogenic domain in hepatitis C virus E2 glycoprotein using a yeast peptide library. Virology200:246–255
    [Google Scholar]
  33. Miriagou V., Argnani R., Kakkanas A., Georgopoulou U., Manservigi R., Mavromara P.. 1995; Expression of the herpes simplex virus type 1 glycoprotein E in human cells and in Escherichia coli : protection studies against lethal viral infection in mice. J Gen Virol76:3137–3143
    [Google Scholar]
  34. Mita E., Hayashi N., Ueda K., Kasahara A., Fusamoto H., Takamizawa A., Matsubara K., Okayama H., Kamada T.. 1992; Expression of MBP-HCV NS1/E2 fusion protein in E. coli and detection of anti-NS1/E2 antibody in type C chronic liver disease. Biochem Biophys Res Commun183:925–930
    [Google Scholar]
  35. Mizushima H., Hijikata M., Asabe S., Hirota M., Kimura K., Shimotohno K.. 1994; Two hepatitis C virus glycoprotein E2 products with different C termini. J Virol68:6215–6222
    [Google Scholar]
  36. Op De Beeck A., Cocquerel L., Dubuisson J.. 2001; Biogenesis of hepatitis C virus envelope glycoproteins. J Gen Virol82:2589–2595
    [Google Scholar]
  37. Pileri P., Uematsu Y., Campagnoli S.. 8 other authors 1998; Binding of hepatitis C virus to CD81. Science282:938–941
    [Google Scholar]
  38. Psichogiou M., Katsoulidou A., Vaindirli E., Francis B., Lee S. R., Hatzakis A.. 1997; Immunologic events during the incubation period of hepatitis C virus infection: the role of antibodies to E2 glycoprotein. Multicentre Hemodialysis Cohort Study on Viral Hepatitis. Transfusion37:858–862
    [Google Scholar]
  39. Reed K. E., Rice C. M.. 2000; Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. Curr Top Microbiol Immunol242:55–84
    [Google Scholar]
  40. Roizman B., Knipe D. M.. 2001; The replication of herpes simplex viruses. In Fields Virology , 4th edn. pp 2399–2459 Edited by Knipe D. M., Howley P. M.. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  41. 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 A87:6547–6549
    [Google Scholar]
  42. Sambrook J., Fritsch E. F., Maniatis T.. 1989; Molecular Cloning: a Laboratory Manual Cold Spring Harbor, NY. Cold Spring Harbor Laboratory;
    [Google Scholar]
  43. Saracco G., Abate M. L., Baldi M.. and others 1994; Hepatitis C virus markers in patients with long-term biochemical and histological remission of chronic hepatitis. Liver14:65–70
    [Google Scholar]
  44. Shad J. A., McHutchison J. G.. 2001; Current and future therapies of hepatitis C. Clin Liver Dis5:335–359
    [Google Scholar]
  45. Siler C. A., McGettigan J. P., Dietzschold B., Herrine S. K., Dubuisson J., Pomerantz R. J., Schnell M. J.. 2002; Live and killed rhabdovirus-based vectors as potential hepatitis C vaccines. Virology292:24–34
    [Google Scholar]
  46. Tsitoura E., Lucas M., Revol-Guyot V., Epstein A. L., Manservigi R., Mavromara P.. 2002; Expression of hepatitis C virus envelope glycoproteins by herpes simplex virus type 1-based amplicon vectors. J Gen Virol83:561–566
    [Google Scholar]
  47. Whitley R. J., Roizman B.. 2001; Herpes simplex virus infections. Lancet357:1513–1518
    [Google Scholar]
  48. Yokosuka O., Omata M., Ito Y., Ohto M.. 1993; Expression of HCV E2/NS1 protein as a fusion protein with maltose binding protein: detection of anti-E2/NS1 antibody in chronic liver disease. Gut34:S64–65
    [Google Scholar]
  49. Yuki N., Hayashi N., Kasahara A., Hagiwara H., Mita E., Ohkawa K., Katayama K., Fusamoto H., Kamada T.. 1996; Quantitative analysis of antibody to hepatitis C virus envelope 2 glycoprotein in patients with chronic hepatitis C virus infection. Hepatology23:947–952
    [Google Scholar]
  50. Zaaijer H. L., Vallari D. S., Cunningham M., Lesniewski R., Reesink H. W., van der Poel C. L., Lelie P. N.. 1994; E2 and NS5: new antigens for detection of hepatitis C virus antibodies. J Med Virol44:395–397
    [Google Scholar]
  51. Zucchelli S., Capone S., Fattori E.. 8 other authors 2000; Enhancing B- and T-cell immune response to a hepatitis C virus E2 DNA vaccine by intramuscular electrical gene transfer. J Virol74:11598–11607
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.18775-0
Loading
/content/journal/jgv/10.1099/vir.0.18775-0
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