Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus.
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-gamma 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-alpha and, together with a suboptimal concentration of Concanavalin A, IFN-gamma 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.
Weber
Olaf
O
BAYER AG Pharmaceutical Division, Antiinfective Research, D-42096 Wuppertal, Germany.
Siegling
Angela
A
BAYER AG Pharmaceutical Division, Antiinfective Research, D-42096 Wuppertal, Germany.
Friebe
Astrid
A
Institute of Medical Immunology, Humboldt University Berlin, Medical School (Charité), Campus Mitte, D-10098 Berlin, Germany.
Limmer
Andreas
A
Zentrum für Molekulare Biologie (ZMBH), Ruprecht Karls University, D-69120 Heidelberg, Germany.
Schlapp
Tobias
T
BAYER AG Animal Health R&D/Bio, Leverkusen, Germany.
Knolle
Percy
P
Zentrum für Molekulare Biologie (ZMBH), Ruprecht Karls University, D-69120 Heidelberg, Germany.
Mercer
Andrew
A
Department of Microbiology, Virus Research Unit, University of Otago, Dunedin, New Zealand.
Schaller
Heinz
H
Zentrum für Molekulare Biologie (ZMBH), Ruprecht Karls University, D-69120 Heidelberg, Germany.
Volk
Hans-Dieter
HD
Institute of Medical Immunology, Humboldt University Berlin, Medical School (Charité), Campus Mitte, D-10098 Berlin, Germany.
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006515:Hepatitis B virus / Q000502:physiology; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009923:Orf virus / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology*; D014779:Virus Replication
D016207:Cytokines; D015164:Vaccines, Inactivated