Inactivated Orf virus (Parapoxvirus ovis) elicits antifibrotic activity in models of liver fibrosis

Aim Inactivated Orf virus (ORFV, Parapoxvirus ovis) demonstrates strong antiviral activity in animal models including a human hepatitis B virus (HBV)‐transgenic mouse. In addition, expression of interferon (IFN)‐γ and interleukin‐10 (IL‐10) was induced after administration of inactivated ORFV in these mice. IFN‐γ and IL‐10 are known to elicit antifibrotic activity. We therefore aimed to study antifibrotic activity of inactivated ORFV in models of liver fibrosis. Methods We characterized ORFV‐induced hepatic cytokine expression in rats. We then studied ORFV in two models of liver fibrosis in rats, pig serum‐induced liver fibrosis and carbon tetrachloride (CCL4)‐induced liver fibrosis. Results ORFV induced hepatic expression of IFN‐γ and IL‐10 in rats. ORFV mediated antifibrotic activity when administrated concomitantly with the fibrosis‐inducing agents in both models of liver fibrosis. Importantly, when CCL4‐induced liver fibrosis was already established, ORFV application still showed significant antifibrotic activity. In addition, we were able to demonstrate a direct antifibrotic effect of ORFV on stellate cells. Conclusion These results establish a potential novel antifibrotic therapeutic approach that not only prevents but also resolves established liver fibrosis. Further studies are required to unravel the details of the mechanisms involved.