title: Inactivated Orf virus (Parapoxvirus ovis) elicits antifibrotic activity in models of liver fibrosis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bayer HealthCare, Wuppertal; Medical Faculty University of Witten-Herdecke, Witten.
authors.forename: Janina
authors.initials: J
authors.lastname: Nowatzky
authors.forename: Andreas
authors.initials: A
authors.lastname: Knorr
authors.forename: Claudia
authors.initials: C
authors.lastname: Hirth-Dietrich
authors.forename: Angela
authors.initials: A
authors.lastname: Siegling
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.forename: Percy
authors.initials: P
authors.lastname: Knolle
authors.forename: Olaf
authors.initials: O
authors.lastname: Weber