Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration.
Identifieur interne : 000D29 ( Main/Exploration ); précédent : 000D28; suivant : 000D30Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration.
Auteurs : Na Li [Singapour] ; Marcus Parrish ; Tze Khee Chan ; Lu Yin ; Prashant Rai ; Yamada Yoshiyuki ; Nona Abolhassani ; Kong Bing Tan ; Orsolya Kiraly ; Vincent T K. Chow ; Bevin P. EngelwardSource :
- Cellular and molecular life sciences : CMLS [ 1420-9071 ] ; 2015.
Descripteurs français
- KwdFr :
- Altération de l'ADN (génétique), Animaux, Cellules rénales canines Madin-Darby, Chiens, Infections à Orthomyxoviridae (génétique), Infections à Orthomyxoviridae (physiopathologie), Lignée cellulaire, Pneumopathie infectieuse (physiopathologie), Pneumopathie infectieuse (virologie), Poumon (physiopathologie), Poumon (virologie), Régénération (génétique), Régénération (physiologie), Réparation de l'ADN (génétique), Sous-type H1N1 du virus de la grippe A, Stress oxydatif (génétique).
- MESH :
- génétique : Altération de l'ADN, Infections à Orthomyxoviridae, Régénération, Réparation de l'ADN, Stress oxydatif.
- physiologie : Régénération.
- physiopathologie : Infections à Orthomyxoviridae, Pneumopathie infectieuse, Poumon.
- virologie : Pneumopathie infectieuse, Poumon.
- Animaux, Cellules rénales canines Madin-Darby, Chiens, Lignée cellulaire, Sous-type H1N1 du virus de la grippe A.
English descriptors
- KwdEn :
- Animals, Cell Line, DNA Damage (genetics), DNA Repair (genetics), Dogs, Influenza A Virus, H1N1 Subtype, Lung (physiopathology), Lung (virology), Madin Darby Canine Kidney Cells, Orthomyxoviridae Infections (genetics), Orthomyxoviridae Infections (physiopathology), Oxidative Stress (genetics), Pneumonia (physiopathology), Pneumonia (virology), Regeneration (genetics), Regeneration (physiology).
- MESH :
- genetics : DNA Damage, DNA Repair, Orthomyxoviridae Infections, Oxidative Stress, Regeneration.
- physiology : Regeneration.
- physiopathology : Lung, Orthomyxoviridae Infections, Pneumonia.
- virology : Lung, Pneumonia.
- Animals, Cell Line, Dogs, Influenza A Virus, H1N1 Subtype, Madin Darby Canine Kidney Cells.
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.
DOI: 10.1007/s00018-015-1879-1
PubMed: 25809161
Affiliations:
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Chow</name></author><author><name sortKey="Engelward, Bevin P" sort="Engelward, Bevin P" uniqKey="Engelward B" first="Bevin P" last="Engelward">Bevin P. Engelward</name></author></analytic><series><title level="j">Cellular and molecular life sciences : CMLS</title><idno type="eISSN">1420-9071</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>DNA Damage (genetics)</term><term>DNA Repair (genetics)</term><term>Dogs</term><term>Influenza A Virus, H1N1 Subtype</term><term>Lung (physiopathology)</term><term>Lung (virology)</term><term>Madin Darby Canine Kidney Cells</term><term>Orthomyxoviridae Infections (genetics)</term><term>Orthomyxoviridae Infections (physiopathology)</term><term>Oxidative Stress (genetics)</term><term>Pneumonia (physiopathology)</term><term>Pneumonia (virology)</term><term>Regeneration (genetics)</term><term>Regeneration (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Altération de l'ADN (génétique)</term><term>Animaux</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>Infections à Orthomyxoviridae (génétique)</term><term>Infections à Orthomyxoviridae (physiopathologie)</term><term>Lignée cellulaire</term><term>Pneumopathie infectieuse (physiopathologie)</term><term>Pneumopathie infectieuse (virologie)</term><term>Poumon (physiopathologie)</term><term>Poumon (virologie)</term><term>Régénération (génétique)</term><term>Régénération (physiologie)</term><term>Réparation de l'ADN (génétique)</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Stress oxydatif (génétique)</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>DNA Damage</term><term>DNA Repair</term><term>Orthomyxoviridae Infections</term><term>Oxidative Stress</term><term>Regeneration</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Altération de l'ADN</term><term>Infections à Orthomyxoviridae</term><term>Régénération</term><term>Réparation de l'ADN</term><term>Stress oxydatif</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Régénération</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Regeneration</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Infections à Orthomyxoviridae</term><term>Pneumopathie infectieuse</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Lung</term><term>Orthomyxoviridae Infections</term><term>Pneumonia</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Pneumopathie infectieuse</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term><term>Pneumonia</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Dogs</term><term>Influenza A Virus, H1N1 Subtype</term><term>Madin Darby Canine Kidney Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules rénales canines Madin-Darby</term><term>Chiens</term><term>Lignée cellulaire</term><term>Sous-type H1N1 du virus de la grippe A</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Singapour</li></country></list><tree><noCountry><name sortKey="Abolhassani, Nona" sort="Abolhassani, Nona" uniqKey="Abolhassani N" first="Nona" last="Abolhassani">Nona Abolhassani</name><name sortKey="Chan, Tze Khee" sort="Chan, Tze Khee" uniqKey="Chan T" first="Tze Khee" last="Chan">Tze Khee Chan</name><name sortKey="Chow, Vincent T K" sort="Chow, Vincent T K" uniqKey="Chow V" first="Vincent T K" last="Chow">Vincent T K. Chow</name><name sortKey="Engelward, Bevin P" sort="Engelward, Bevin P" uniqKey="Engelward B" first="Bevin P" last="Engelward">Bevin P. Engelward</name><name sortKey="Kiraly, Orsolya" sort="Kiraly, Orsolya" uniqKey="Kiraly O" first="Orsolya" last="Kiraly">Orsolya Kiraly</name><name sortKey="Parrish, Marcus" sort="Parrish, Marcus" uniqKey="Parrish M" first="Marcus" last="Parrish">Marcus Parrish</name><name sortKey="Rai, Prashant" sort="Rai, Prashant" uniqKey="Rai P" first="Prashant" last="Rai">Prashant Rai</name><name sortKey="Tan, Kong Bing" sort="Tan, Kong Bing" uniqKey="Tan K" first="Kong Bing" last="Tan">Kong Bing Tan</name><name sortKey="Yin, Lu" sort="Yin, Lu" uniqKey="Yin L" first="Lu" last="Yin">Lu Yin</name><name sortKey="Yoshiyuki, Yamada" sort="Yoshiyuki, Yamada" uniqKey="Yoshiyuki Y" first="Yamada" last="Yoshiyuki">Yamada Yoshiyuki</name></noCountry><country name="Singapour"><noRegion><name sortKey="Li, Na" sort="Li, Na" uniqKey="Li N" first="Na" last="Li">Na Li</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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