ARTICLE ABSTRACT
								DOI: 10.1099/vir.0.19138-0
								Online 30 April 2003

Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus

Olaf Weber,¹ Angela Siegling,¹ Astrid Friebe,² Andreas Limmer,³ Tobias Schlapp,⁴ Percy Knolle,³ Andrew Mercer,⁵ Heinz Schaller³ and Hans-Dieter Volk²

¹BAYER AG Pharmaceutical Division, Antiinfective Research, D-42096 Wuppertal, Germany
²Institute of Medical Immunology, Humboldt University Berlin, Medical School (Charité), Campus Mitte, D-10098 Berlin, Germany
³Zentrum für Molekulare Biologie (ZMBH), Ruprecht Karls University, D-69120 Heidelberg, Germany
⁴BAYER AG Animal Health R&D/Bio, Leverkusen, Germany
⁵Department of Microbiology, Virus Research Unit, University of Otago, Dunedin, New Zealand

It is known that some viruses are able to induce vigorous immune reactions. This study shows that inactivated parapoxvirus ovis (Orf virus), 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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This article is now available in the July 2003 print issue of JGV (vol. 84, 1843–1852). The complete issue of the journal may be seen in electronic form on JGV Online.