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

Weber, Olaf; Siegling, Angela; Friebe, Astrid; Limmer, Andreas; Schlapp, Tobias; Knolle, Percy A.; Mercer, Andrew A.; Schaller, Heinz; Volk, Hans‐Dieter

doi:10.1099/vir.0.19138-0

Cited by 53 publications

(90 citation statements)

References 30 publications

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“…Furthermore, PPVO was able to reduce lethality in mice infected with herpes simplex virus. This effect also was not accompanied by a tissue-damaging inflammatory response or other side effects (36).…”

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confidence: 82%

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Immunomodulatory Effects of Inactivated Parapoxvirus Ovis (Orf Virus) on Human Peripheral Immune Cells: Induction of Cytokine Secretion in Monocytes and Th1-Like Cells

Friebe

Siegling

Friederichs

et al. 2004

J Virol

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Inactivated parapoxvirus ovis (Orf virus;Parapoxvirus ovis (Orf virus; PPVO) is a member of the poxvirus family and causes pustular skin lesions in sheep, goats, and humans (20). The family of poxviruses consists of large DNA viruses with strong immunogenic properties. To evade the host immune defense, poxviruses utilize a variety of immunomodulatory cellular proteins, which enable them to replicate in spite of an active immune response (1,16,17,28). Such proteins have been described for PPVO; these include a viral interleukin 10 (IL-10) homologue (11, 12), a granulocyte-macrophage colony-stimulating factor, an IL-2-inhibiting protein (8), and the product of a gene with homology to the vaccinia virus E3L gene, which counteracts interferon-induced cell resistance (18,19,21,30).The immunostimulating and modulating capacities made PPVO an interesting candidate for new antiviral strategies (36). The immunomodulatory properties of the virus could be used by means of a noninfectious preparation of inactivated PPVO to influence the clinical course of other viral infections. Thus, inactivated PPVO showed strong effects in several animal models for acute and chronic virus infections. It was effective in a guinea pig model for genital herpes disease and in a transgenic mouse model for human hepatitis B virus (HBV). In HBVtransgenic mice, PPVO led to a reduction in virus replication that was not associated with the destruction of liver cells. Furthermore, PPVO was able to reduce lethality in mice infected with herpes simplex virus. This effect also was not accompanied by a tissue-damaging inflammatory response or other side effects (36).Investigations of the cytokine expression profiles of animals treated with PPVO implicate gamma interferon (IFN-␥) as a key mediator of the PPVO-mediated activity against HBV and herpes simplex virus. Thus, the application of PPVO first led to the release of Th1-inducing or effector cytokines, such as IL-12, IL-18, and IFN-␥. The neutralization of IFN-␥ by antibodies could abolish antiviral effects in vivo. The induction of type 1 cytokines was followed by the secretion of anti-inflammatory cytokines, such as IL-4 (36). These findings indicate the induction of a limited immune response and offer an explanation for the good tolerability of the preparation in animals. The immunomodulatory properties of PPVO might be responsible for the observed antiviral effects and might contribute to the absence of systemic side effects and the absence of tissue injury that are observed after the direct administration of Th1-inducing or effector cytokines.The aim of this study was to investigate whether the effects of PPVO can be determined under controlled conditions in human immune cells. In the work presented, we evaluated the cytokine secretion of peripheral blood cells, especially IFN-␥, which has been proved in animal models to be an important factor in transducing antiviral effects. In addition, we evaluated the mechanisms that mediate the effects of PPVO.

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confidence: 82%

“…The immunostimulating and modulating capacities made PPVO an interesting candidate for new antiviral strategies (36). The immunomodulatory properties of the virus could be used by means of a noninfectious preparation of inactivated PPVO to influence the clinical course of other viral infections.…”

mentioning

confidence: 99%

Immunomodulatory Effects of Inactivated Parapoxvirus Ovis (Orf Virus) on Human Peripheral Immune Cells: Induction of Cytokine Secretion in Monocytes and Th1-Like Cells

Friebe

Siegling

Friederichs

et al. 2004

J Virol

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“…The efficacy of PPVO as an antiviral immunotherapy for the treatment of specific infections has also been demonstrated. Weber et al (2003) showed that Balb/c mice treated intraperitoneally with PPVO were protected from a lethal intranasal challenge with Herpes simplex virus. Similarly, PPVO treatment reduced the severity of herpes disease in guinea pigs and the degree of Hepatitis B virus replication in a transgenic mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…Its currently approved indication is to reduce herpesvirus respiratory infections in horses. It is well documented that some viruses induce vigorous immune reactions (Weber et al 2003;Ziebell et al 1997). …”

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confidence: 99%

Effects of inactivated Parapoxvirus ovis on polymorphonuclear leukocyte function and myeloperoxidase activity in horses

Ülgen¹,

Yarami̇s²,

Rayaman³

et al. 2014

Vet. Med. - Czech

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ABSTRACT:Immunomodulatory products have been used for years in veterinary medicine. Inactivated Parapoxvirus ovis (iPPVO) is currently used in equine medicine as an immunomodulator to improve the immune system and as a prophylactic treatment to prevent or treat infectious diseases. This study was designed to determine the effects of iPPVO on polymorphonuclear leukocyte (PMNL) function (phagocytosis and intracellular killing activity) and the myeloperoxidase (MPO) activity of PMNLs in horses. Twenty-four healthy English thoroughbred horses with an average age of 11 years were included in the study. Venous blood samples (10 ml) were taken before (agentfree controls) and after the administration of iPPVO (2 ml i.m. injection on Days 1, 3, and 5). PMNLs (1 × 10 7 cells/ml) were isolated from venous blood containing EDTA (0.1 g/ml) with Ficoll-Hypaque gradient centrifugation. Cellular phagocytosis and intracellular killing activities were assayed using a modification of Alexander's method before and after treatment with iPPVO. MPO activity was also measured. The administration of iPPVO significantly increased the phagocytic, intracellular killing, and MPO activities of equine PMNLs (P = 0.0058, P = 0.0050, and P = 0.0070, respectively). This study demonstrates a strong correlation between MPO activity and PMNL function. The administration of iPPVO to horses has a supportive effect on their cellular immunity and an immunomodulatory effect against equine viral infections.

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“…The immunostimulatory capacities of PPVO have been demonstrated in various mouse models (Büttner and Mayr, 1986;Mayr et al, 1978). (Weber et al, 2003). In dogs, another non-permissive species for infection with PPVO, antibody production has been demonstrated after intramuscular injection followed by intra-dermal administration of an attenuated PPVO strain (Büttner et al, 75 1995).…”

Section: Introductionmentioning

confidence: 99%

Specific antibodies induced by inactivated parapoxvirus ovis potently enhance oxidative burst in canine blood polymorphonuclear leukocytes and monocytes

Schütze

Raue

Büttner³

et al. 2010

Veterinary Microbiology

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

Cited by 53 publications

References 30 publications

Immunomodulatory Effects of Inactivated Parapoxvirus Ovis (Orf Virus) on Human Peripheral Immune Cells: Induction of Cytokine Secretion in Monocytes and Th1-Like Cells

Immunomodulatory Effects of Inactivated Parapoxvirus Ovis (Orf Virus) on Human Peripheral Immune Cells: Induction of Cytokine Secretion in Monocytes and Th1-Like Cells

Effects of inactivated Parapoxvirus ovis on polymorphonuclear leukocyte function and myeloperoxidase activity in horses

Specific antibodies induced by inactivated parapoxvirus ovis potently enhance oxidative burst in canine blood polymorphonuclear leukocytes and monocytes

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