{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:24:33Z","timestamp":1745468673575,"version":"3.40.4"},"reference-count":22,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intervirology"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> Recombination-activating gene (<i>Rag<\/i>) 1 and <i>Rag2<\/i>, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. <b><i>Method:<\/i><\/b> We investigated the effects of <i>Rag2<\/i> deficiency in clustered regularly interspaced short palindromic repeats\/Cas9-mediated FVB-<i>Rag2<\/i> knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. <b><i>Results:<\/i><\/b> MAV-1 infection caused more severe histopathological changes in FVB-<i>Rag2<\/i> KO mice than in WT mice. FVB-<i>Rag2<\/i> KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-<i>Rag2<\/i> KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1\u03b1, induced protein 10, interferon (IFN)-\u03b1, IFN-\u03b3, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-<i>Rag2<\/i> KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-<i>Rag2<\/i> KO mice than in WT mice. <b><i>Conclusion:<\/i><\/b> In mice, <i>Rag2<\/i> deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases. <\/jats:p>","DOI":"10.1159\/000520463","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T22:00:31Z","timestamp":1636063231000},"page":"134-143","source":"Crossref","is-referenced-by-count":0,"title":["Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection"],"prefix":"10.1159","volume":"65","author":[{"given":"Han-Kyul","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-Min","family":"Seo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Woong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eui-Suk","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang-Kyu","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.11.2.231"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13699"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4689-4699.2005"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1219-1223.1998"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9180"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.11.018"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90760-5"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1126\/science.2360047"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5295.2094"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00375-08"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01678"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2017.06.005"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.11.5584-5590.2004"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.20.10518-10523.2002"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1203644"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.59.1.61"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006327200"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.4.1449"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)80590-3"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0027"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/s1044-5323(02)00125-2"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-5699(97)80019-9"}],"container-title":["Intervirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/520463","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/520463","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:29:44Z","timestamp":1745422184000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000520463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":22,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,7,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000520463","archive":["Portico"],"relation":{},"ISSN":["0300-5526","1423-0100"],"issn-type":[{"type":"print","value":"0300-5526"},{"type":"electronic","value":"1423-0100"}],"subject":[],"published":{"date-parts":[[2021,11,4]]}}}