title: Antiviral effects of pan-caspase inhibitors on the replication of coxsackievirus B3.
abstract: The induction of apoptosis during coxsackievirus B3 (CVB3) infection is well documented. In order to study whether the inhibition of apoptosis has an impact on CVB3 replication, the pan-caspase inhibitor Z-VAD-FMK was used. The decreased CVB3 replication is based on reduced accumulation of both viral RNA and viral proteins. These effects are due to an inhibitory influence of Z-VAD-FMK on the proteolytic activity of the CVB3 proteases 2A and 3C, which was demonstrated by using the target protein poly(A)-binding protein (PABP). The antiviral effect of the structurally different pan-caspase inhibitor Q-VD-OPH was independently of the viral protease inhibition and resulted in suppression of virus progeny production and impaired release of newly produced CVB3 from infected cells. A delayed release of cytochrome c into the cytoplasm was detected in Q-VD-OPH-treated CVB3-infected cells pointing to an involvement of caspases in the initial steps of mitochondrial membrane-permeabilization.
authors.affiliation: Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Jena, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Martin
authors.forename: Nadine
authors.initials: N
authors.lastname: Jarasch
authors.forename: Matthias
authors.initials: M
authors.lastname: Nestler
authors.forename: Alexander
authors.initials: A
authors.lastname: Rassmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Munder
authors.forename: Simone
authors.initials: S
authors.lastname: Seitz
authors.forename: Roland
authors.initials: R
authors.lastname: Zell
authors.forename: Peter
authors.initials: P
authors.lastname: Wutzler
authors.forename: Andreas
authors.initials: A
authors.lastname: Henke
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003384:Coxsackievirus Infections; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D029822:Enterovirus B, Human / Q000502:physiology*; D006801:Humans; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D014764:Viral Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; D020169:Caspases