Your browser doesn't support javascript.
loading
Oncolytic Reovirus Infection Is Facilitated by the Autophagic Machinery.
Kemp, Vera; Dautzenberg, Iris J C; Limpens, Ronald W; van den Wollenberg, Diana J M; Hoeben, Rob C.
Afiliação
  • Kemp V; Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. v.kemp@lumc.nl.
  • Dautzenberg IJC; Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. i.j.c.dautzenberg@lumc.nl.
  • Limpens RW; Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. r.w.a.l.limpens@lumc.nl.
  • van den Wollenberg DJM; Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. d.j.m.van_den_wollenberg@lumc.nl.
  • Hoeben RC; Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. r.c.hoeben@lumc.nl.
Viruses ; 9(10)2017 09 21.
Article em En | MEDLINE | ID: mdl-28934149
Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as a stand-alone therapy remains to be improved. The success of future trials can be greatly influenced by the identification and the regulation of the cellular pathways that are important for reovirus replication and oncolysis. Here, we demonstrate that reovirus induces autophagy in several cell lines, evident from the formation of Atg5-Atg12 complexes, microtubule-associated protein 1 light chain 3 (LC3) lipidation, p62 degradation, the appearance of acidic vesicular organelles, and LC3 puncta. Furthermore, in electron microscopic images of reovirus-infected cells, autophagosomes were observed without evident association with viral factories. Using UV-inactivated reovirus, we demonstrate that a productive reovirus infection facilitates the induction of autophagy. Importantly, knock-out cell lines for specific autophagy-related genes revealed that the expression of Atg3 and Atg5 but not Atg13 facilitates reovirus replication. These findings highlight a central and Atg13-independent role for the autophagy machinery in facilitating reovirus infection and contribute to a better understanding of reovirus-host interactions.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reoviridae / Autofagia / Replicação Viral / Infecções por Reoviridae / Vírus Oncolíticos / Autofagossomos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Viruses Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reoviridae / Autofagia / Replicação Viral / Infecções por Reoviridae / Vírus Oncolíticos / Autofagossomos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Viruses Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Holanda