title: Avian reovirus-triggered apoptosis enhances both virus spread and the processing of the viral nonstructural muNS protein.
abstract: Avian reovirus non-structural protein muNS is partially cleaved in infected chicken embryo fibroblast cells to produce a 55-kDa carboxyterminal protein, termed muNSC, and a 17-kDa aminoterminal polypeptide, designated muNSN. In this study we demonstrate that muNS processing is catalyzed by a caspase 3-like protease activated during the course of avian reovirus infection. The cleavage site was mapped by site directed mutagenesis between residues Asp-154 and Ala-155 of the muNS sequence. Although muNS and muNSC, but not muNSN, are able to form inclusions when expressed individually in transfected cells, only muNS is able to recruit specific ARV proteins to these structures. Furthermore, muNSC associates with ARV factories more weakly than muNS, sigmaNS and lambdaA. Finally, the inhibition of caspase activity in ARV-infected cells does not diminish ARV gene expression and replication, but drastically reduces muNS processing and the release and dissemination of progeny viral particles.
authors.affiliation: Centro de Investigación en Química Biológica y Materiales Moleculares, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Grille
authors.affiliation: Centro de Investigación en Química Biológica y Materiales Moleculares, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Busch
authors.affiliation: Centro de Investigación en Química Biológica y Materiales Moleculares, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Martínez-Costas
authors.affiliation: Centro de Investigación en Química Biológica y Materiales Moleculares, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: franciscojavier.benavente@usc.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Benavente
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D005347:Fibroblasts / Q000821:virology; D054884:Host-Pathogen Interactions; D030101:Orthoreovirus, Avian / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D053148:Caspase 3
keywords: Apoptosis; Avian reovirus; Caspase; Proteolytic processing; Viroplasms; Virus spread; muNS
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