{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:50:19Z","timestamp":1791395419181,"version":"4.3.3"},"reference-count":80,"publisher":"Microbiology Society","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82171736"],"award-info":[{"award-number":["82171736"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82472272"],"award-info":[{"award-number":["82472272"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:p>Viruses often hijack core host cell processes to optimize their replication. In the current study, we conducted comparative proteomics analyses of epithelial cells infected by the prevalent human pathogen herpes simplex virus type 2 (HSV-2), followed by experimental validation. The results reveal that HSV-2 infection induces significant reprogramming of the host cell cycle, characterized by a pronounced accumulation of cells in the synthesis (S)-phase. Mechanistically, we discovered that HSV-2 promotes gap 1 (G1)\/S transition by downregulating the cyclin-dependent kinase inhibitor p21 via a proteasome-mediated pathway. Following this, the virus induces S-phase cell cycle arrest, characterized by reduced levels of cyclin-dependent kinase 2 (CDK2) and its active phosphorylated form and decreased activity of the cyclin A2\u2013CDK2 complex. Consequently, this dysfunctional \u2018pseudo-S-phase\u2019 state significantly enhances HSV-2 replication. These findings reveal a previously unrecognized dual mechanism employed by HSV-2 to manipulate the host cell cycle, thereby advancing our understanding of how pathogens disrupt cellular homeostasis to facilitate their replication.<\/jats:p>","DOI":"10.1099\/jgv.0.002346","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:17:36Z","timestamp":1791389856000},"source":"Crossref","is-referenced-by-count":0,"title":["Herpes simplex virus type 2 induces S-phase entry and arrest to regulate the cell cycle for efficient replication"],"prefix":"10.1099","volume":"107","author":[{"given":"Huimin","family":"Wang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranqing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuncheng","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"He","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longchao","family":"Xu","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"},{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binlian","family":"Sun","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"},{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4594-9215","authenticated-orcid":false,"given":"Qinxue","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"},{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5164-5891","authenticated-orcid":false,"given":"Mudan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China"},{"name":"Medical School, University of Chinese Academy of Sciences, Beijing 100049, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003268"},{"key":"R2","volume-title":"The Cell: A Molecular Approach","author":"Cooper","year":"2000"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-857-9:113"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2736-5_1"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.04.003"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2021.01.010"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2022.06.007"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27554"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1515\/jbcpp-2014-0018"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-01831-9"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0888-2_10"},{"key":"R12","first-page":"103","article-title":"The cell cycle, cyclin-dependent kinases, and viral infections: new horizons and unexpected connections","volume":"5","author":"Schang","year":"2003","journal-title":"Prog Cell Cycle Res"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.3390\/v14020431"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13811"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.0146"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90141-9"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.0147"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09529-y"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1186\/1747-1028-4-1"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.3390\/v12030303"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06078-4"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2024-056307"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.1982373"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00660-22"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.77.2.851-861.2003"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.10.4475-4481.2001"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.3390\/v16101601"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81261-1"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17146-z"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208616"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401538"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000418"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-02640-5"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00510-23"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03717-5"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03870-x"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27124-8"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-06-0372"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704723105"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43495-6"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1038\/366701a0"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2016.04.008"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013921"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.168013"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2003.11.009"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1996.0020"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-0602-4_25"},{"key":"R48","first-page":"1","article-title":"Relationship between the proteasomal system and autophagy","volume":"4","author":"Lilienbaum","year":"2013","journal-title":"Int J Biochem Mol Biol"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.026"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05135.x"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.13.1.261"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.216922"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202513542"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109334118"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01403-y"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr3673"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123327"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1038\/35055073"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.2144\/01306rv01"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2736-5_9"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02080-z"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02000-3"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8245-8255.1999"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.11.9456-9467.1999"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050587597"},{"key":"R66","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.034405-0"},{"key":"R67","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90409-8"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.7.4509-4516.1996"},{"key":"R69","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.04.013"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.02.011"},{"key":"R71","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3382"},{"key":"R72","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205102"},{"key":"R73","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.14.2120"},{"key":"R74","doi-asserted-by":"publisher","DOI":"10.1101\/gad.949802"},{"key":"R75","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-4615-1_4"},{"key":"R76","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01885-18"},{"key":"R77","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2022.2029329"},{"key":"R78","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.1175"},{"key":"R79","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.8.4005-4016.2006"},{"key":"R80","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-12-3341"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.002346?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:17:40Z","timestamp":1791389860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.002346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":80,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,7]]}},"URL":"https:\/\/doi.org\/10.1099\/jgv.0.002346","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}