Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.
Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.
AiCuris GmbH & Co.KG, Wuppertal, Germany.
Daniela
D
Paulsen
Andreas
A
Urban
Andreas
A
Knorr
Claudia
C
Hirth-Dietrich
Angela
A
Siegling
Hans-Dieter
HD
Volk
Andrew A
AA
Mercer
Andreas
A
Limmer
Beatrix
B
Schumak
Percy
P
Knolle
Helga
H
Ruebsamen-Schaeff
Olaf
O
Weber
D000818:Animals; D016174:Hepacivirus / Q000472:pathogenicity*; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D008103:Liver Cirrhosis / Q000517:prevention & control / Q000821:virology*; D008297:Male; D051379:Mice; D009923:Orf virus / Q000502:physiology*; D051381:Rats; D013552:Swine