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Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization

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...

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Autores principales: Song, Xiaowei, Wang, Yiliang, Li, Feng, Cao, Wenyan, Zeng, Qiongzhen, Qin, Shurong, Wang, Zhaoyang, Jia, Jiaoyan, Xiao, Ji, Hu, Xiao, Liu, Kaisheng, Wang, Yifei, Ren, Zhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785254/
https://www.ncbi.nlm.nih.gov/pubmed/35082770
http://dx.doi.org/10.3389/fmicb.2021.799890
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author Song, Xiaowei
Wang, Yiliang
Li, Feng
Cao, Wenyan
Zeng, Qiongzhen
Qin, Shurong
Wang, Zhaoyang
Jia, Jiaoyan
Xiao, Ji
Hu, Xiao
Liu, Kaisheng
Wang, Yifei
Ren, Zhe
author_facet Song, Xiaowei
Wang, Yiliang
Li, Feng
Cao, Wenyan
Zeng, Qiongzhen
Qin, Shurong
Wang, Zhaoyang
Jia, Jiaoyan
Xiao, Ji
Hu, Xiao
Liu, Kaisheng
Wang, Yifei
Ren, Zhe
author_sort Song, Xiaowei
collection PubMed
description 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 via 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.
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spelling pubmed-87852542022-01-25 Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization Song, Xiaowei Wang, Yiliang Li, Feng Cao, Wenyan Zeng, Qiongzhen Qin, Shurong Wang, Zhaoyang Jia, Jiaoyan Xiao, Ji Hu, Xiao Liu, Kaisheng Wang, Yifei Ren, Zhe Front Microbiol Microbiology 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 via 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. Frontiers Media S.A. 2022-01-10 /pmc/articles/PMC8785254/ /pubmed/35082770 http://dx.doi.org/10.3389/fmicb.2021.799890 Text en Copyright © 2022 Song, Wang, Li, Cao, Zeng, Qin, Wang, Jia, Xiao, Hu, Liu, Wang and Ren. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Song, Xiaowei
Wang, Yiliang
Li, Feng
Cao, Wenyan
Zeng, Qiongzhen
Qin, Shurong
Wang, Zhaoyang
Jia, Jiaoyan
Xiao, Ji
Hu, Xiao
Liu, Kaisheng
Wang, Yifei
Ren, Zhe
Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
title Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
title_full Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
title_fullStr Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
title_full_unstemmed Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
title_short Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
title_sort hsp90 inhibitors inhibit the entry of herpes simplex virus 1 into neuron cells by regulating cofilin-mediated f-actin reorganization
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785254/
https://www.ncbi.nlm.nih.gov/pubmed/35082770
http://dx.doi.org/10.3389/fmicb.2021.799890
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