Baz-Martínez, MaiteSilva Álvarez, Sabela daRodríguez, EstefaníaGuerra Varela, JorgeEl Motiam, AhmedVidal Figueroa, AnxoGarcía-Caballero Parada, TomásGonzález Barcia, MiguelSánchez Piñón, LauraMuñoz Fontela, CesarCollado Rodríguez, ManuelRivas Vázquez, Carmen2020-06-062020-06-062016Baz-Martínez, M., Da Silva-Álvarez, S., Rodríguez, E. et al. Cell senescence is an antiviral defense mechanism. Sci Rep 6, 37007 (2016). https://doi.org/10.1038/srep37007http://hdl.handle.net/10347/22869Cellular 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.eng© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/journal article10.1038/srep370072045-2322open access