Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication

Human coronavirus (HCoV) similar to other viruses rely on host cell machinery for both replication and to spread. The p97/VCP ATPase is associated with diverse pathways that may favor HCoV replication. In this study, we assessed the role of p97 and associated host responses in human lung cell line H...

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Autores principales:	Kai-Wen Cheng, Shan Li, Feng Wang, Nallely M. Ruiz-Lopez, Nadia Houerbi, Tsui-Fen Chou
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	coronavirus p97 ATPase proteomics inhibitor Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/40fe4a94fc7f42a7b79bd4b240b002e6
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spelling	oai:doaj.org-article:40fe4a94fc7f42a7b79bd4b240b002e62021-11-25T17:09:45ZImpacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication10.3390/cells101129532073-4409https://doaj.org/article/40fe4a94fc7f42a7b79bd4b240b002e62021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2953https://doaj.org/toc/2073-4409Human coronavirus (HCoV) similar to other viruses rely on host cell machinery for both replication and to spread. The p97/VCP ATPase is associated with diverse pathways that may favor HCoV replication. In this study, we assessed the role of p97 and associated host responses in human lung cell line H1299 after HCoV-229E or HCoV-OC43 infection. Inhibition of p97 function by small molecule inhibitors shows antiviral activity, particularly at early stages of the virus life cycle, during virus uncoating and viral RNA replication. Importantly, p97 activity inhibition protects human cells against HCoV-induced cytopathic effects. The p97 knockdown also inhibits viral production in infected cells. Unbiased quantitative proteomics analyses reveal that HCoV-OC43 infection resulted in proteome changes enriched in cellular senescence and DNA repair during virus replication. Further analysis of protein changes between infected cells with control and p97 shRNA identifies cell cycle pathways for both HCoV-229E and HCoV-OC43 infection. Together, our data indicate a role for the essential host protein p97 in supporting HCoV replication, suggesting that p97 is a therapeutic target to treat HCoV infection.Kai-Wen ChengShan LiFeng WangNallely M. Ruiz-LopezNadia HouerbiTsui-Fen ChouMDPI AGarticlecoronavirusp97ATPaseproteomicsinhibitorBiology (General)QH301-705.5ENCells, Vol 10, Iss 2953, p 2953 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	coronavirus p97 ATPase proteomics inhibitor Biology (General) QH301-705.5
spellingShingle	coronavirus p97 ATPase proteomics inhibitor Biology (General) QH301-705.5 Kai-Wen Cheng Shan Li Feng Wang Nallely M. Ruiz-Lopez Nadia Houerbi Tsui-Fen Chou Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication
description	Human coronavirus (HCoV) similar to other viruses rely on host cell machinery for both replication and to spread. The p97/VCP ATPase is associated with diverse pathways that may favor HCoV replication. In this study, we assessed the role of p97 and associated host responses in human lung cell line H1299 after HCoV-229E or HCoV-OC43 infection. Inhibition of p97 function by small molecule inhibitors shows antiviral activity, particularly at early stages of the virus life cycle, during virus uncoating and viral RNA replication. Importantly, p97 activity inhibition protects human cells against HCoV-induced cytopathic effects. The p97 knockdown also inhibits viral production in infected cells. Unbiased quantitative proteomics analyses reveal that HCoV-OC43 infection resulted in proteome changes enriched in cellular senescence and DNA repair during virus replication. Further analysis of protein changes between infected cells with control and p97 shRNA identifies cell cycle pathways for both HCoV-229E and HCoV-OC43 infection. Together, our data indicate a role for the essential host protein p97 in supporting HCoV replication, suggesting that p97 is a therapeutic target to treat HCoV infection.
format	article
author	Kai-Wen Cheng Shan Li Feng Wang Nallely M. Ruiz-Lopez Nadia Houerbi Tsui-Fen Chou
author_facet	Kai-Wen Cheng Shan Li Feng Wang Nallely M. Ruiz-Lopez Nadia Houerbi Tsui-Fen Chou
author_sort	Kai-Wen Cheng
title	Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication
title_short	Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication
title_full	Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication
title_fullStr	Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication
title_full_unstemmed	Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication
title_sort	impacts of p97 on proteome changes in human cells during coronaviral replication
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/40fe4a94fc7f42a7b79bd4b240b002e6
work_keys_str_mv	AT kaiwencheng impactsofp97onproteomechangesinhumancellsduringcoronaviralreplication AT shanli impactsofp97onproteomechangesinhumancellsduringcoronaviralreplication AT fengwang impactsofp97onproteomechangesinhumancellsduringcoronaviralreplication AT nallelymruizlopez impactsofp97onproteomechangesinhumancellsduringcoronaviralreplication AT nadiahouerbi impactsofp97onproteomechangesinhumancellsduringcoronaviralreplication AT tsuifenchou impactsofp97onproteomechangesinhumancellsduringcoronaviralreplication
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Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication

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