{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T20:13:42Z","timestamp":1783368822560,"version":"3.54.6"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"publisher","award":["31900141"],"award-info":[{"award-number":["31900141"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"publisher","award":["31472218"],"award-info":[{"award-number":["31472218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"publisher","award":["KJQN202022"],"award-info":[{"award-number":["KJQN202022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["31900141"],"award-info":[{"award-number":["31900141"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["31472218"],"award-info":[{"award-number":["31472218"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["KJQN202022"],"award-info":[{"award-number":["KJQN202022"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)","award":["31900141"],"award-info":[{"award-number":["31900141"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)","award":["31472218"],"award-info":[{"award-number":["31472218"]}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)","award":["KJQN202022"],"award-info":[{"award-number":["KJQN202022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>DNA damage response (DDR) is an evolutionarily conserved mechanism by which eukaryotic cells sense DNA lesions caused by intrinsic and extrinsic stimuli, including virus infection. Although interactions between DNA viruses and DDR have been extensively studied, how RNA viruses, especially coronaviruses, regulate DDR remains unknown. A previous study showed that the porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the Coronaviridae family, induces DDR in infected cells. However, the underlying mechanism was unclear. This study showed that PEDV activates the ATM-Chk2 signaling, while inhibition of ATM or Chk2 dampens the early stage of PEDV infection. Additionally, we found that PEDV-activated ATM signaling correlates with intracellular ROS production. Interestingly, we showed that, unlike the typical \u03b3H2AX foci, PEDV infection leads to a unique \u03b3H2AX staining pattern, including phase I (nuclear ring staining), II (pan-nuclear staining), and III (co-staining with apoptotic bodies), which highly resembles the apoptosis process. Furthermore, we demonstrated that PEDV-induced H2AX phosphorylation depends on the activation of caspase-7 and caspase-activated DNAse (CAD), but not ATM-Chk2. Finally, we showed that the knockdown of H2AX attenuates PEDV replication. Taken together, we conclude that PEDV induces DDR through the ROS-ATM and caspase7-CAD-\u03b3H2AX signaling pathways to foster its early replication.<\/jats:p>","DOI":"10.3390\/v14081782","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T03:40:32Z","timestamp":1660621232000},"page":"1782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-\u03b3H2AX Signaling Pathways to Foster Its Replication"],"prefix":"10.3390","volume":"14","author":[{"given":"Xin","family":"Ming","sequence":"first","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Zhao","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liumei","family":"Sun","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"Jiangsu Key Laboratory of Sericultural Biology and Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caisheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-4924","authenticated-orcid":false,"given":"Hyun-Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5473-2002","authenticated-orcid":false,"given":"Jeong-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Sam","family":"Jung","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-5010","authenticated-orcid":false,"given":"Yingjuan","family":"Qian","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Foreign Expert Workshop, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"Jiangsu Key Laboratory for High-Tech Research and Development of Veterinary Biopharmaceuticals, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/35044005","article-title":"The DNA damage response: Putting checkpoints in perspective","volume":"408","author":"Zhou","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.molmed.2006.07.007","article-title":"DNA damage-induced cell death by apoptosis","volume":"12","author":"Roos","year":"2006","journal-title":"Trends Mol. 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