{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:41:49Z","timestamp":1767847309854,"version":"3.49.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Herpes simplex virus 1 (HSV-1) is a common neurotropic virus, the herpes simplex encephalitis (HSE) caused by which is considered to be the most common sporadic but fatal encephalitis. Traditional antiviral drugs against HSV-1 are limited to nucleoside analogs targeting viral factors. Inhibition of heat shock protein 90 (Hsp90) has potent anti-HSV-1 activities <jats:italic>via<\/jats:italic> numerous mechanisms, but the effects of Hsp90 inhibitors on HSV-1 infection in neuronal cells, especially in the phase of virus entry, are still unknown. In this study, we aimed to investigate the effects of the Hsp90 inhibitors on HSV-1 infection of neuronal cells. Interestingly, we found that Hsp90 inhibitors promoted viral adsorption but inhibited subsequent penetration in neuronal cell lines and primary neurons, which jointly confers the antiviral activity of the Hsp90 inhibitors. Mechanically, Hsp90 inhibitors mainly impaired the interaction between Hsp90 and cofilin, resulting in reduced cofilin membrane distribution, which led to F-actin polymerization to promote viral attachment. However, excessive polymerization of F-actin inhibited subsequent viral penetration. Consequently, unidirectional F-actin polymerization limits the entry of HSV-1 virions into neuron cells. Our research extended the molecular mechanism of Hsp90 in HSV-1 infection in neuron cells and provided a theoretical basis for developing antiviral drugs targeting Hsp90.<\/jats:p>","DOI":"10.3389\/fmicb.2021.799890","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T12:39:23Z","timestamp":1641818363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiaowei","family":"Song","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongzhen","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shurong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaoyan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaisheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-53168-7_1","article-title":"Initial contact: the first steps in herpesvirus entry","author":"Azab","year":"2017","journal-title":"Cell Biology of Herpes Viruses"},{"key":"B2","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S1474-4422(18)30316-8","article-title":"Herpes viruses and Alzheimer\u2019s disease: new evidence in the debate.","volume":"17","author":"Balin","year":"2018","journal-title":"Lancet Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/nrm3609","article-title":"Functions of cofilin in cell locomotion and invasion.","volume":"14","author":"Bravo-Cordero","year":"2013","journal-title":"Nat. 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