title: Cell senescence is an antiviral defense mechanism.
abstract: Cellular senescence is often considered a protection mechanism triggered by conditions that impose cellular stress. Continuous proliferation, DNA damaging agents or activated oncogenes are well-known activators of cell senescence. Apart from a characteristic stable cell cycle arrest, this response also involves a proinflammatory phenotype known as senescence-associated secretory phenotype (SASP). This, together with the widely known interference with senescence pathways by some oncoviruses, had led to the hypothesis that senescence may also be part of the host cell response to fight virus. Here, we evaluate this hypothesis using vesicular stomatitis virus (VSV) as a model. Our results show that VSV replication is significantly impaired in both primary and tumor senescent cells in comparison with non-senescent cells, and independently of the stimulus used to trigger senescence. Importantly, we also demonstrate a protective effect of senescence against VSV in vivo. Finally, our results identify the SASP as the major contributor to the antiviral defense exerted by cell senescence in vitro, and points to a role activating and recruiting the immune system to clear out the infection. Thus, our study indicates that cell senescence has also a role as a natural antiviral defense mechanism.
authors.affiliation: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Baz-Martínez
authors.affiliation: Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Sergas, Santiago de Compostela, E15706, Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Da Silva-Álvarez
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Departamento de Genética. Facultad de Veterinaria, Universidade de Santiago de Compostela, Campus de Lugo, Lugo, E27002, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Guerra
authors.affiliation: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Motiam
authors.affiliation: Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15782, Spain.
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Departamento de Ciencias Morfológicas, Facultad de Medicina. USC. Complejo Hospitalario de Santiago (CHUS), Sergas, E15706 Santiago de Compostela, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: García-Caballero
authors.affiliation: Departamento de Farmacia, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Travesía Choupana s/n, Santiago de Compostela E15706, Spain.|Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII), Sergas, Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: González-Barcia
authors.affiliation: Departamento de Genética. Facultad de Veterinaria, Universidade de Santiago de Compostela, Campus de Lugo, Lugo, E27002, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sánchez
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Hamburg, Germany.
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.affiliation: Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Sergas, Santiago de Compostela, E15706, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Collado
authors.affiliation: Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, E15706, Spain.|Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Darwin 3, Madrid 28049, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rivas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D006801:Humans; D007107:Immune System / Q000502:physiology*; D051379:Mice; D012692:Serial Passage; D054243:Vesicular Stomatitis / Q000276:immunology / Q000517:prevention & control*; D018116:Vesiculovirus / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication
chemical_list: D000970:Antineoplastic Agents