2024-03-28T08:34:24Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1510442022-05-05T07:43:16Zcom_10261_22com_10261_1col_10261_275
Induction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus
Martínez, Isidoro
García-Carpizo, Verónica
Navarro, Diego
Aranda, Ana
Zambrano, Alberto
Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
DNA damage
Human respiratory
ROS
Syncytial virus
Cellular senescence
Human respiratory syncytial virus (HRSV) accounts for the majority of lower respiratory tract infections during infancy and childhood and is associated with significant morbidity and mortality. HRSV provokes a proliferation arrest and characteristic syncytia in cellular systems such as immortalized epithelial cells. We show here that HRSV induces the expression of DNA damage markers and proliferation arrest such as P-TP53, P-ATM, CDKN1A and γH2AFX in cultured cells secondary to the production of mitochondrial reactive oxygen species (ROS). The DNA damage foci contained γH2AFX and TP53BP1, indicative of double-strand breaks (DSBs) and could be reversed by antioxidant treatments such as N-Acetylcysteine (NAC) or reduced glutathione ethyl ester (GSHee). The damage observed is associated with the accumulation of senescent cells, displaying a canonical senescent phenotype in both mononuclear cells and syncytia. In addition, we show signs of DNA damage and aging such as γH2AFX and CDKN2A expression in the respiratory epithelia of infected mice long after viral clearance. Altogether, these results show that HRSV triggers a DNA damage-mediated cellular senescence program probably mediated by oxidative stress. The results also suggest that this program might contribute to the physiopathology of the infection, tissue remodeling and aging, and might be associated to long-term consequences of HRSV infections.
This work was supported by Grants MPY-1038/14 to Alberto Zambrano, PI 11/00590 to Isidoro Martínez and RD12/0036/0030 to Ana Aranda from FIS (Instituto de Salud Carlos III) and Grant BFU2011-28958, from Ministerio de Economía y Competitividad to Ana Aranda.
Peer Reviewed
2017-06-08T06:58:12Z
2017-06-08T06:58:12Z
2016
2017-06-08T06:58:13Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1080/21505594.2016.1144001
e-issn: 2150-5608
issn: 2150-5594
Virulence 7(4): 427-442 (2016)
http://hdl.handle.net/10261/151044
10.1080/21505594.2016.1144001
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100004587
26809688
Sí
none
Taylor & Francis