The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus.

2.50
Hdl Handle:
http://hdl.handle.net/10033/213695
Title:
The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus.
Authors:
von Hahn, Thomas; Schulze, Andreas; Chicano Wust, Ivan; Heidrich, Benjamin; Becker, Thomas; Steinmann, Eike; Helfritz, Fabian A; Rohrmann, Katrin; Urban, Stephan; Manns, Michael P; Pietschmann, Thomas; Ciesek, Sandra
Abstract:
The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients.
Affiliation:
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Citation:
The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus. 2011, 6 (9):e24142 PLoS ONE
Journal:
PloS one
Issue Date:
2011
URI:
http://hdl.handle.net/10033/213695
DOI:
10.1371/journal.pone.0024142
PubMed ID:
21909416
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the Dept. experimental virology

Full metadata record

DC FieldValue Language
dc.contributor.authorvon Hahn, Thomasen
dc.contributor.authorSchulze, Andreasen
dc.contributor.authorChicano Wust, Ivanen
dc.contributor.authorHeidrich, Benjaminen
dc.contributor.authorBecker, Thomasen
dc.contributor.authorSteinmann, Eikeen
dc.contributor.authorHelfritz, Fabian Aen
dc.contributor.authorRohrmann, Katrinen
dc.contributor.authorUrban, Stephanen
dc.contributor.authorManns, Michael Pen
dc.contributor.authorPietschmann, Thomasen
dc.contributor.authorCiesek, Sandraen
dc.date.accessioned2012-03-01T10:28:46Z-
dc.date.available2012-03-01T10:28:46Z-
dc.date.issued2011-
dc.identifier.citationThe novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus. 2011, 6 (9):e24142 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid21909416-
dc.identifier.doi10.1371/journal.pone.0024142-
dc.identifier.urihttp://hdl.handle.net/10033/213695-
dc.description.abstractThe pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients.en
dc.language.isoenen
dc.subject.meshCalcineurinen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCyclosporineen
dc.subject.meshHepacivirusen
dc.subject.meshHepatitis B virusen
dc.subject.meshHumansen
dc.subject.meshImmunosuppressive Agentsen
dc.subject.meshProtein Kinase Cen
dc.subject.meshProtein Kinase Inhibitorsen
dc.subject.meshPyrrolesen
dc.subject.meshQuinazolinesen
dc.subject.meshRNA, Viralen
dc.subject.meshVirus Internalizationen
dc.subject.meshVirus Replicationen
dc.titleThe novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus.en
dc.typeArticleen
dc.contributor.departmentDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.en
dc.identifier.journalPloS oneen

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