{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:15:27Z","timestamp":1758399327246},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,9,13]],"date-time":"2012-09-13T00:00:00Z","timestamp":1347494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2013,5]]},"abstract":"Aim<\/jats:title>Inactivated Orf<\/jats:italic><\/jats:styled-content> virus (ORFV<\/jats:styled-content>, Parapoxvirus ovis<\/jats:italic><\/jats:styled-content>) demonstrates strong antiviral activity in animal models including a human hepatitis B<\/jats:styled-content> virus (HBV<\/jats:styled-content>)\u2010transgenic mouse. In addition, expression of interferon (IFN<\/jats:styled-content>)\u2010\u03b3 and interleukin\u201010 (IL<\/jats:styled-content>\u201010) was induced after administration of inactivated ORFV<\/jats:styled-content> in these mice. IFN<\/jats:styled-content>\u2010\u03b3 and IL<\/jats:styled-content>\u201010 are known to elicit antifibrotic activity. We therefore aimed to study antifibrotic activity of inactivated ORFV<\/jats:styled-content> in models of liver fibrosis.<\/jats:p><\/jats:sec>Methods<\/jats:title>We characterized ORFV<\/jats:styled-content>\u2010induced hepatic cytokine expression in rats. We then studied ORFV<\/jats:styled-content> in two models of liver fibrosis in rats, pig serum\u2010induced liver fibrosis and carbon tetrachloride (CCL<\/jats:styled-content>4<\/jats:sub>)\u2010induced liver fibrosis.<\/jats:p><\/jats:sec>Results<\/jats:title>ORFV<\/jats:styled-content> induced hepatic expression of IFN<\/jats:styled-content>\u2010\u03b3 and IL<\/jats:styled-content>\u201010 in rats. ORFV<\/jats:styled-content> mediated antifibrotic activity when administrated concomitantly with the fibrosis\u2010inducing agents in both models of liver fibrosis. Importantly, when CCL<\/jats:styled-content>4<\/jats:sub>\u2010induced liver fibrosis was already established, ORFV<\/jats:styled-content> application still showed significant antifibrotic activity. In addition, we were able to demonstrate a direct antifibrotic effect of ORFV<\/jats:styled-content> on stellate cells.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1872-034x.2012.01086.x","type":"journal-article","created":{"date-parts":[[2012,9,13]],"date-time":"2012-09-13T06:49:08Z","timestamp":1347518948000},"page":"535-546","source":"Crossref","is-referenced-by-count":11,"title":["Inactivated Orf<\/i><\/scp> virus (Parapoxvirus ovis<\/i><\/scp>) elicits antifibrotic activity in models of liver fibrosis"],"prefix":"10.1111","volume":"43","author":[{"given":"Janina","family":"Nowatzky","sequence":"first","affiliation":[{"name":"Bayer HealthCare Wuppertal"},{"name":"Medical Faculty University of Witten\u2010Herdecke Witten"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Knorr","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Wuppertal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Hirth\u2010Dietrich","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Wuppertal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Siegling","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Wuppertal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Dieter","family":"Volk","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology and Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT) Charit\u00e9 \u2013 Medical University Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Limmer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Experimental Immunology University Hospital Bonn Bonn"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Percy","family":"Knolle","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Experimental Immunology University Hospital Bonn Bonn"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Weber","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Wuppertal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130246"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60383-9"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(68)90111-3"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.01.009"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.4.548"},{"key":"e_1_2_5_8_1","first-page":"582","article-title":"Reversal of hepatic fibrosis \u2013 fact or fantasy?","volume":"432","author":"Friedman SL","year":"2006","journal-title":"Hepatology"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711796391679"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2011.02.011"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2011.02.005"},{"key":"e_1_2_5_12_1","first-page":"311","article-title":"Ovine disease. 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