Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-08

AUTHORS

Na Li, Marcus Parrish, Tze Khee Chan, Lu Yin, Prashant Rai, Yamada Yoshiyuki, Nona Abolhassani, Kong Bing Tan, Orsolya Kiraly, Vincent T. K. Chow, Bevin P. Engelward

ABSTRACT

Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of 2 weeks in vivo. We show that influenza induces DNA damage to both, when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67-positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DNA double strand break (DSB) repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA damage both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome. More... »

PAGES

2973-2988

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00018-015-1879-1

    DOI

    http://dx.doi.org/10.1007/s00018-015-1879-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041130704

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25809161


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