1887

Abstract

It is known that some viruses are able to induce vigorous immune reactions. This study shows that inactivated parapoxvirus ovis (), strain D1701 (PPVO), induces an autoregulatory cytokine response that involves the upregulation of IL-12, IL-18, IFN- and other T helper 1-type cytokines and their subsequent downregulation, which is accompanied by induction of IL-4. An increase in IL-10 expression was also found in the livers of PPVO-treated mice. PPVO protects mice from lethal herpes simplex virus type 1 infection and guinea pigs from recurrent genital herpes disease. With dosages as low as 500 000 virus particles, PPVO is more potent than the current standard 3TC therapy in hepatitis B virus transgenic mice. No signs of inflammation or any other side effects were observed. PPVO induces IL-12, TNF- and, together with a suboptimal concentration of Concanavalin A, IFN- in human peripheral blood leukocytes as well. The principle of an autoregulatory cytokine induction by an inactivated virus might have advantages over existing immune therapies and it is concluded that inactivated PPVO should be investigated further for its potential use in antiviral therapy.

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2003-07-01
2019-10-16
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References

  1. Bahnemann, H. G. ( 1990; ). Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine. Vaccine 8, 299–303.[CrossRef]
    [Google Scholar]
  2. Binder, G. K. & Griffin, D. E. ( 2001; ). Interferon-γ-mediated site-specific clearance of alphavirus from CNS neurons. Interferon-γ-mediated site-specific clearance of alphavirus from CNS neurons. Science 293, 303–306.[CrossRef]
    [Google Scholar]
  3. Büttner, M., Czerny, C. P., Lehner, K. H. & Wertz K. ( 1995; ). Interferon induction in peripheral blood mononuclear leukocytes of man and farm animals by poxvirus vector candidates and some poxvirus constructs. Vet Immunol Immunopathol 46, 237–250.[CrossRef]
    [Google Scholar]
  4. Cavanaugh, V. J., Guidotti, L. G. & Chisari, F. V. ( 1997; ). Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. J Virol 71, 3236–3243.
    [Google Scholar]
  5. Cavanaugh, V. J., Guidotti, L. G. & Chisari, F. V. ( 1998; ). Inhibition of hepatitis B virus replication during adenovirus and cytomegalovirus infections in transgenic mice. J Virol 72, 2630–2637.
    [Google Scholar]
  6. Deane, D., McInnes, C. J., Percival, A. & 7 other authors ( 2000; ). Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2. J Virol 74, 1313–1320.[CrossRef]
    [Google Scholar]
  7. del Val, M., Hengel, H., Häcker, H., Hartlaub, U., Ruppert, T., Lucin, P. & Koszinowski, U. H. ( 1992; ). Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. J Exp Med 176, 729–738.[CrossRef]
    [Google Scholar]
  8. Fleming, S. B., McCaughan, C. A., Andrews, A. E., Nash, A. D. & Mercer, A. A. ( 1997; ). A homolog of interleukin-10 is encoded by the poxvirus orf virus. J Virol 71, 4857–4861.
    [Google Scholar]
  9. Förster, R., Wolf, G. & Mayr, A. ( 1994; ). Highly attenuated poxviruses induce functional priming of neutrophils in vitro. Arch Virol 136, 219–226.[CrossRef]
    [Google Scholar]
  10. Grandvaux, N., tenOever, B. R., Servant, M. J. & Hiscott, J. ( 2002; ). The interferon antiviral response: from viral invasion to evasion. Curr Opin Infect Dis 1, 259–267.
    [Google Scholar]
  11. Guidotti, L. G. & Chisari, F. V. ( 1996; ). Current Opinion in Immunology, vol. 8, pp. 487–483. Edited by R. Zinkernagel & B. Bloom. London: Current Biology.
  12. Guidotti, L. G., Borrow, P., Hobbs, M. V., Matzke, B., Gresser, I., Oldstone, M. B. A. & Chisari, F. V. ( 1996; ). Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. Proc Natl Acad Sci U S A 93, 4589–4594.[CrossRef]
    [Google Scholar]
  13. Guidotti, L. G., Rochford, R., Chung, J., Shapiro, M., Purcell, R. & Chisari, F. V. ( 1999; ). Viral clearance without destruction of infected cells during acute HBV infection. Science 284, 825–829.[CrossRef]
    [Google Scholar]
  14. Haig, D. M. & Mercer, A. A. ( 1998; ). Ovine disease. Orf. Vet Res 29, 311–326.
    [Google Scholar]
  15. Haig, D. M. & McInnes, C. J. ( 2002; ). Immunity and counter-immunity during infection with the parapoxvirus orf virus. Virus Res 88, 3–16.[CrossRef]
    [Google Scholar]
  16. Haig, D., McInnes, C., Deane, D. & 8 other authors ( 1996; ). Cytokines and their inhibitors in orf virus infection. Vet Immunol Immunopathol 54, 261–267.[CrossRef]
    [Google Scholar]
  17. Haig, D., McInnes, C. J., Deane, D., Reid, H. W. & Mercer, A. A. ( 1997; ). The immune and inflammatory response to orf virus. Comp Immunol Microbiol Infect Dis 20, 197–204.[CrossRef]
    [Google Scholar]
  18. Haig, D. M., McInnes, C. J., Thomson, J., Wood, A., Bunyan, K. & Mercer, A. A. ( 1998; ). The orf virus OV20.0L gene product is involved in interferon resistance and inhibits an interferon-inducible, double stranded RNA-dependent kinase. Immunology 93, 335–340.
    [Google Scholar]
  19. Kimura, K., Kakimi, K., Wieland, S., Guidotti, L. G. & Chisari, F. V. ( 2002; ). Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice. J Virol 76, 10702–10707.[CrossRef]
    [Google Scholar]
  20. Knolle, P. A., Uhrig, A., Hegenbarth, S., Loser, E., Schmitt, E., Gerken, G. & Lohse, A. W. ( 1998; ). IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules. Clin Exp Immunol 114, 427–433.[CrossRef]
    [Google Scholar]
  21. Kruse, N. & Weber, O. ( 2001; ). Selective induction of apoptosis in antigen-presenting cells in mice by Parapoxvirus ovis. J Virol 75, 4699–4704.[CrossRef]
    [Google Scholar]
  22. Lane, H. C., Depper, J. M., Greene, W. C., Whalen, G., Waldmann, T. A. & Fauci, A. S. ( 1985; ). Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. New Engl J Med 2, 79–84.
    [Google Scholar]
  23. Leite-de-Moraes, M. C., Hameg, A., Pacilio, M., Koezuka, Y., Taniguchi, M., Van Kaer, L., Schneider, E., Dy, M. & Herbelin A. ( 2000; ). IL-18 enhances IL-4 production by ligand-activated NKT lymphocytes: a pro-Th2 effect of IL-18 exerted through NKT cells. J Immunol 166, 945–951.
    [Google Scholar]
  24. Marsig, E. & Stickl, H. ( 1988; ). Highly attenuated poxviruses induce functional priming of neutrophils in vitro. Zentralbl Veterinarmed B 35, 601–609 (in German).
    [Google Scholar]
  25. Mayr, A., Büttner, M., Wolf, G., Meyer, H. & Czerny, C. ( 1989; ). Experimental detection of the paraspecific effects of purified and inactivated poxviruses. Zentralbl Veterinarmed B 36, 81–99 (in German).[CrossRef]
    [Google Scholar]
  26. McKeever, D. J., Jenkinson, D. M., Hutchinson, G. & Reid, H. W. ( 1988; ). Studies on the pathogenesis of orf virus infection in sheep. J Comp Pathol 99, 317–328.[CrossRef]
    [Google Scholar]
  27. Micallef, M. J., Ohtsuki, T., Kohno, K. & 9 other authors ( 1996; ). Interferon-γ-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-γ production. Eur J Immunol 26, 1647–1651.[CrossRef]
    [Google Scholar]
  28. Mocarski, E. S., Jr ( 2002; ). Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion. Trends Microbiol 10, 332–339.[CrossRef]
    [Google Scholar]
  29. Mossman, K. L. ( 2002; ). Activation and inhibition of virus and interferon: the herpesvirus story. Viral Immunol 15, 3–15.[CrossRef]
    [Google Scholar]
  30. Schijns, V. E. C. J., Haagmans, B. L., Wierda, C. M. H., Kruithof, B., Heijnen, I. A. F. M., Alber, G. & Horzinek, M. C. ( 1998; ). Mice lacking IL-12 develop polarized Th1 cells during viral infection. J Immunol 160, 3958–3964.
    [Google Scholar]
  31. Siegling, A., Lehmann, M., Platzer, C., Emmrich, F. & Volk, H. D. ( 1994; ). A novel multispecific competitor fragment for quantitative PCR analysis of cytokine gene expression in rats. J Immunol Methods 177, 23–28.[CrossRef]
    [Google Scholar]
  32. Smeltz, R. B., Chen, J., Hu-Li, J. & Shevach, E. M. ( 2001; ). Regulation of interleukin (IL)-18 receptor α chain expression on CD4+ T cells during T helper (Th)1/Th2 differentiation: critical downregulatory role of IL-4. J Exp Med 194, 143–153.[CrossRef]
    [Google Scholar]
  33. Weber, O., Schlemmer, K. H., Hartmann, E. & 10 other authors ( 2002; ). Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model. Antiviral Res 54, 69–75.[CrossRef]
    [Google Scholar]
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