{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:02:16Z","timestamp":1780624936914,"version":"3.54.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":85,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program, Ministry of Science and Technology of China","award":["2024YFC2310003"],"award-info":[{"award-number":["2024YFC2310003"]}]},{"name":"Key Research and Development Program, Ministry of Science and Technology of China","award":["2022YFC2303502"],"award-info":[{"award-number":["2022YFC2303502"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32222022"],"award-info":[{"award-number":["32222022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92354301"],"award-info":[{"award-number":["92354301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Flaviviridae Dengue virus (DENV) and Zika virus (ZIKV) have posed significant threats to global public health in the past decades. Despite extensive study on therapeutic strategies against these viruses, effective treatment options are still lacking. Within host cells, the cytoskeletal vimentin intermediate filament network facilitates viral replication during DENV and ZIKV infection by shrinking and forming a cage-like structure. Our previous work indicated that MEK1\/2 inhibitors can induce the dispersion of vimentin, but their potential impact on flavivirus infection remains unclear. Here, we observed that the MEK1\/2 signaling pathway is activated in host cells infected with DENV and ZIKV. Treatment with MEK1\/2 inhibitors significantly impaired the replication of both viruses. Further mechanistic studies revealed that MEK1\/2 inhibitors prevent viral infection by promoting the dispersion of intracellular vimentin network, thereby disrupting the cytoskeletal structure required for viral replication. Our findings not only expand the understanding of vimentin regulatory mechanisms from a cellular biology perspective but also provide a new perspective on MEK1\/2 inhibition as a potential anti-DENV and anti-ZIKV strategy.<\/jats:p>","DOI":"10.1093\/jmcb\/mjaf037","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T11:55:43Z","timestamp":1761134143000},"source":"Crossref","is-referenced-by-count":1,"title":["MEK1\/2 inhibition prevents DENV and ZIKV infection via disrupting the cytoskeletal vimentin cage required for viral replication"],"prefix":"10.1093","volume":"17","author":[{"given":"Yuhan","family":"Huang","sequence":"first","affiliation":[{"name":"Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiageng","family":"Lu","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]},{"name":"School of Life Science and Technology, ShanghaiTech University , Shanghai 201210 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhi","family":"Cui","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]},{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Sun","sequence":"additional","affiliation":[{"name":"International Research Center for Marine Biosciences, Shanghai Ocean University , Shanghai 201306 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8601-8820","authenticated-orcid":false,"given":"Yaming","family":"Jiu","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]},{"name":"School of Life Science and Technology, ShanghaiTech University , Shanghai 201210 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"2026030905113898400_bib1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.antiviral.2014.09.004","article-title":"MEK\/ERK activation plays a decisive role in yellow fever virus replication: implication as an antiviral therapeutic target","volume":"111","author":"Albarnaz","year":"2014","journal-title":"Antiviral Res."},{"key":"2026030905113898400_bib2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ijid.2020.08.008","article-title":"DENV and ZIKV detection in patients with acute febrile syndrome in C\u00f3rdoba, Colombia","volume":"99","author":"Avil\u00e9s-Vergara","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"2026030905113898400_bib3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1743-422X-8-11","article-title":"Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum","volume":"8","author":"Bhattacharyya","year":"2011","journal-title":"Virol. J."},{"key":"2026030905113898400_bib4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.virol.2016.12.011","article-title":"Viral exploitation of the MEK\/ERK pathway\u2014a tale of vaccinia virus and other viruses","volume":"507","author":"Bonjardim","year":"2017","journal-title":"Virology"},{"key":"2026030905113898400_bib5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2026030905113898400_bib6","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3390\/vaccines8030530","article-title":"The molecular interactions of ZIKV and DENV with the type-I IFN response","volume":"8","author":"Coldbeck-Shackley","year":"2020","journal-title":"Vaccines"},{"key":"2026030905113898400_bib7","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.chom.2020.11.003","article-title":"Integrative imaging reveals SARS-CoV-2-induced reshaping of subcellular morphologies","volume":"28","author":"Cortese","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2026030905113898400_bib8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3390\/cells7100147","article-title":"Vimentin diversity in health and disease","volume":"7","author":"Danielsson","year":"2018","journal-title":"Cells"},{"key":"2026030905113898400_bib9","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.bbrc.2017.11.177","article-title":"Trametinib suppresses HIV-1 replication by interfering with the disassembly of human immunodeficiency virus type 1 capsid core","volume":"495","author":"Dochi","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026030905113898400_bib10","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.3390\/ijms20143427","article-title":"Human DNA virus exploitation of the MAPK\u2013ERK cascade","volume":"20","author":"DuShane","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2026030905113898400_bib11","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3390\/v8060098","article-title":"Identification of vimentin as a potential therapeutic target against HIV infection","volume":"8","author":"Fern\u00e1ndez-Ortega","year":"2016","journal-title":"Viruses"},{"key":"2026030905113898400_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-020-01025-7","article-title":"MEK inhibitors for the treatment of non-small cell lung cancer","volume":"14","author":"Han","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"2026030905113898400_bib13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.pharmthera.2018.02.007","article-title":"ERK1\/2 inhibitors: new weapons to inhibit the RAS-regulated RAF\u2013MEK1\/2\u2013ERK1\/2 pathway","volume":"187","author":"Kidger","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"2026030905113898400_bib14","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1177\/1753425910377799","article-title":"Mitogen-activated protein kinases p38 and ERK1\/2 regulated control of Mycobacterium avium replication in primary murine macrophages is independent of tumor necrosis factor-\u03b1 and interleukin-10","volume":"17","author":"Klug","year":"2011","journal-title":"Innate Immun."},{"key":"2026030905113898400_bib15","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1007\/s12013-013-9665-x","article-title":"ROCK is involved in vimentin phosphorylation and rearrangement induced by dengue virus","volume":"67","author":"Lei","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"2026030905113898400_bib16","first-page":"2299","article-title":"An Epstein\u2013Barr virus transforming protein associates with vimentin in lymphocytes","volume":"7","author":"Liebowitz","year":"1987","journal-title":"Mol. Cell. Biol."},{"key":"2026030905113898400_bib17","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1128\/JVI.01410-15","article-title":"Epstein\u2013Barr virus (EBV) tegument protein BGLF2 promotes EBV reactivation through activation of the p38 mitogen-activated protein kinase","volume":"90","author":"Liu","year":"2015","journal-title":"J. Virol."},{"key":"2026030905113898400_bib18","doi-asserted-by":"crossref","first-page":"101304","DOI":"10.1016\/j.coviro.2023.101304","article-title":"MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases","volume":"59","author":"Ludwig","year":"2023","journal-title":"Curr. Opin. Virol."},{"key":"2026030905113898400_bib19","doi-asserted-by":"crossref","first-page":"a011254","DOI":"10.1101\/cshperspect.a011254","article-title":"MAP kinase pathways","volume":"4","author":"Morrison","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2026030905113898400_bib20","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.4049\/jimmunol.170.12.6234","article-title":"Corneal IL-8 expression following adenovirus infection is mediated by c-Src activation in human corneal fibroblasts","volume":"170","author":"Natarajan","year":"2003","journal-title":"J. Immunol."},{"key":"2026030905113898400_bib21","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1139\/cjm-2020-0572","article-title":"Dengue virus: epidemiology, biology, and disease aetiology","volume":"67","author":"Roy","year":"2021","journal-title":"Can. J. Microbiol."},{"key":"2026030905113898400_bib22","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.antiviral.2018.07.006","article-title":"The clinically approved MEK inhibitor Trametinib efficiently blocks influenza A virus propagation and cytokine expression","volume":"157","author":"Schr\u00e4der","year":"2018","journal-title":"Antiviral Res."},{"key":"2026030905113898400_bib23","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1074\/jbc.M107322200","article-title":"HIV Nef increases T cell ERK MAP kinase activity","volume":"277","author":"Schrager","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2026030905113898400_bib24","doi-asserted-by":"crossref","first-page":"16557","DOI":"10.1073\/pnas.2002828117","article-title":"Dissecting the mechanism of signaling-triggered nuclear export of newly synthesized influenza virus ribonucleoprotein complexes","volume":"117","author":"Schreiber","year":"2020","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026030905113898400_bib25","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1158\/0008-5472.CAN-05-1484","article-title":"Adenovirus-induced extracellular signal-regulated kinase phosphorylation during the late phase of infection enhances viral protein levels and virus progeny","volume":"66","author":"Sch\u00fcmann","year":"2006","journal-title":"Cancer Res."},{"key":"2026030905113898400_bib26","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1128\/jvi.60.3.1186-1191.1986","article-title":"Progressive reorganization of the host cell cytoskeleton during adenovirus infection","volume":"60","author":"Staufenbiel","year":"1986","journal-title":"J. Virol."},{"key":"2026030905113898400_bib27","doi-asserted-by":"crossref","first-page":"17982","DOI":"10.1073\/pnas.0809698105","article-title":"Stimulation of Ebola virus production from persistent infection through activation of the Ras\/MAPK pathway","volume":"105","author":"Strong","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026030905113898400_bib28","doi-asserted-by":"crossref","first-page":"106823","DOI":"10.1016\/j.vph.2020.106823","article-title":"SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells","volume":"137","author":"Suzuki","year":"2021","journal-title":"Vascul. Pharmacol."},{"key":"2026030905113898400_bib29","doi-asserted-by":"crossref","first-page":"e2113909119","DOI":"10.1073\/pnas.2113909119","article-title":"Host cytoskeletal vimentin serves as a structural organizer and an RNA-binding protein regulator to facilitate Zika viral replication","volume":"119","author":"Zhang","year":"2022","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026030905113898400_bib30","doi-asserted-by":"crossref","first-page":"mjae009","DOI":"10.1093\/jmcb\/mjae009","article-title":"Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling","volume":"16","author":"Zhao","year":"2024","journal-title":"J. Mol. Cell Biol."},{"key":"2026030905113898400_bib31","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/s41467-023-36123-w","article-title":"Salmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection","volume":"14","author":"Zhao","year":"2023","journal-title":"Nat. Commun."}],"container-title":["Journal of Molecular Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jmcb\/advance-article-pdf\/doi\/10.1093\/jmcb\/mjaf037\/64942487\/mjaf037.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jmcb\/article-pdf\/17\/8\/mjaf037\/64942487\/mjaf037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jmcb\/article-pdf\/17\/8\/mjaf037\/64942487\/mjaf037.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:11:48Z","timestamp":1773047508000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jmcb\/article\/doi\/10.1093\/jmcb\/mjaf037\/8301231"}},"subtitle":[],"editor":[{"given":"Xuebiao","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,3,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jmcb\/mjaf037","relation":{},"ISSN":["1674-2788","1759-4685"],"issn-type":[{"value":"1674-2788","type":"print"},{"value":"1759-4685","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,8]]},"article-number":"mjaf037"}}