Cargando…
The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry
Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610886/ https://www.ncbi.nlm.nih.gov/pubmed/37896778 http://dx.doi.org/10.3390/v15102001 |
_version_ | 1785128362220453888 |
---|---|
author | Yuan, Xiao Zhang, Xiaoman Wang, Huan Mao, Xiang Sun, Yingjie Tan, Lei Song, Cuiping Qiu, Xusheng Ding, Chan Liao, Ying |
author_facet | Yuan, Xiao Zhang, Xiaoman Wang, Huan Mao, Xiang Sun, Yingjie Tan, Lei Song, Cuiping Qiu, Xusheng Ding, Chan Liao, Ying |
author_sort | Yuan, Xiao |
collection | PubMed |
description | Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the IBV and PEDV life cycles was investigated. When the UPS was suppressed by pharmacological inhibition at the early infection stage, IBV and PEDV infectivity were severely impaired. Further study showed that inhibition of UPS did not change the internalization of virus particles; however, by using R18 and DiOC-labeled virus particles, we found that inhibition of UPS prevented the IBV and PEDV membrane fusion with late endosomes or lysosomes. In addition, proteasome inhibitors blocked the degradation of the incoming viral protein N, suggesting the uncoating process and genomic RNA release were suppressed. Subsequently, the initial translation of genomic RNA was blocked. Thus, UPS may target the virus-cellular membrane fusion to facilitate the release of incoming viruses from late endosomes or lysosomes, subsequently blocking the following virus uncoating, initial translation, and replication events. Similar to the observation of proteasome inhibitors, ubiquitin-activating enzyme E1 inhibitor PYR-41 also impaired the entry of IBV, enhanced the accumulation of ubiquitinated proteins, and depleted mono-ubiquitin. In all, this study reveals an important role of UPS in coronavirus entry by preventing membrane fusion and identifies UPS as a potential target for developing antiviral therapies for coronavirus. |
format | Online Article Text |
id | pubmed-10610886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106108862023-10-28 The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry Yuan, Xiao Zhang, Xiaoman Wang, Huan Mao, Xiang Sun, Yingjie Tan, Lei Song, Cuiping Qiu, Xusheng Ding, Chan Liao, Ying Viruses Article Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the IBV and PEDV life cycles was investigated. When the UPS was suppressed by pharmacological inhibition at the early infection stage, IBV and PEDV infectivity were severely impaired. Further study showed that inhibition of UPS did not change the internalization of virus particles; however, by using R18 and DiOC-labeled virus particles, we found that inhibition of UPS prevented the IBV and PEDV membrane fusion with late endosomes or lysosomes. In addition, proteasome inhibitors blocked the degradation of the incoming viral protein N, suggesting the uncoating process and genomic RNA release were suppressed. Subsequently, the initial translation of genomic RNA was blocked. Thus, UPS may target the virus-cellular membrane fusion to facilitate the release of incoming viruses from late endosomes or lysosomes, subsequently blocking the following virus uncoating, initial translation, and replication events. Similar to the observation of proteasome inhibitors, ubiquitin-activating enzyme E1 inhibitor PYR-41 also impaired the entry of IBV, enhanced the accumulation of ubiquitinated proteins, and depleted mono-ubiquitin. In all, this study reveals an important role of UPS in coronavirus entry by preventing membrane fusion and identifies UPS as a potential target for developing antiviral therapies for coronavirus. MDPI 2023-09-26 /pmc/articles/PMC10610886/ /pubmed/37896778 http://dx.doi.org/10.3390/v15102001 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yuan, Xiao Zhang, Xiaoman Wang, Huan Mao, Xiang Sun, Yingjie Tan, Lei Song, Cuiping Qiu, Xusheng Ding, Chan Liao, Ying The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry |
title | The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry |
title_full | The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry |
title_fullStr | The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry |
title_full_unstemmed | The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry |
title_short | The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry |
title_sort | ubiquitin-proteasome system facilitates membrane fusion and uncoating during coronavirus entry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610886/ https://www.ncbi.nlm.nih.gov/pubmed/37896778 http://dx.doi.org/10.3390/v15102001 |
work_keys_str_mv | AT yuanxiao theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT zhangxiaoman theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT wanghuan theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT maoxiang theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT sunyingjie theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT tanlei theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT songcuiping theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT qiuxusheng theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT dingchan theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT liaoying theubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT yuanxiao ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT zhangxiaoman ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT wanghuan ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT maoxiang ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT sunyingjie ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT tanlei ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT songcuiping ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT qiuxusheng ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT dingchan ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry AT liaoying ubiquitinproteasomesystemfacilitatesmembranefusionanduncoatingduringcoronavirusentry |