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VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection

β-coronaviruses reshape host cell endomembranes to form double-membrane vesicles (DMVs) for genome replication and transcription. Ectopically expressed viral nonstructural proteins nsp3 and nsp4 interact to zipper and bend the ER for DMV biogenesis. Genome-wide screens revealed the autophagy protein...

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Autores principales: Ji, Mingming, Li, Meng, Sun, Long, Zhao, Hongyu, Li, Ying, Zhou, Lulu, Yang, Zhenni, Zhao, Xin, Qu, Wenyan, Xue, Hanbing, Zheng, Ze, Li, Yiming, Deng, Hongyu, Zhao, Yan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097365/
https://www.ncbi.nlm.nih.gov/pubmed/35536318
http://dx.doi.org/10.1083/jcb.202112081
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author Ji, Mingming
Li, Meng
Sun, Long
Zhao, Hongyu
Li, Ying
Zhou, Lulu
Yang, Zhenni
Zhao, Xin
Qu, Wenyan
Xue, Hanbing
Zheng, Ze
Li, Yiming
Deng, Hongyu
Zhao, Yan G.
author_facet Ji, Mingming
Li, Meng
Sun, Long
Zhao, Hongyu
Li, Ying
Zhou, Lulu
Yang, Zhenni
Zhao, Xin
Qu, Wenyan
Xue, Hanbing
Zheng, Ze
Li, Yiming
Deng, Hongyu
Zhao, Yan G.
author_sort Ji, Mingming
collection PubMed
description β-coronaviruses reshape host cell endomembranes to form double-membrane vesicles (DMVs) for genome replication and transcription. Ectopically expressed viral nonstructural proteins nsp3 and nsp4 interact to zipper and bend the ER for DMV biogenesis. Genome-wide screens revealed the autophagy proteins VMP1 and TMEM41B as important host factors for SARS-CoV-2 infection. Here, we demonstrated that DMV biogenesis, induced by virus infection or expression of nsp3/4, is impaired in the VMP1 KO or TMEM41B KO cells. In VMP1 KO cells, the nsp3/4 complex forms normally, but the zippered ER fails to close into DMVs. In TMEM41B KO cells, the nsp3–nsp4 interaction is reduced and DMV formation is suppressed. Thus, VMP1 and TMEM41B function at different steps during DMV formation. VMP1 was shown to regulate cross-membrane phosphatidylserine (PS) distribution. Inhibiting PS synthesis partially rescues the DMV defects in VMP1 KO cells, suggesting that PS participates in DMV formation. We provide molecular insights into the collaboration of host factors with viral proteins to remodel host organelles.
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spelling pubmed-90973652022-12-06 VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection Ji, Mingming Li, Meng Sun, Long Zhao, Hongyu Li, Ying Zhou, Lulu Yang, Zhenni Zhao, Xin Qu, Wenyan Xue, Hanbing Zheng, Ze Li, Yiming Deng, Hongyu Zhao, Yan G. J Cell Biol Report β-coronaviruses reshape host cell endomembranes to form double-membrane vesicles (DMVs) for genome replication and transcription. Ectopically expressed viral nonstructural proteins nsp3 and nsp4 interact to zipper and bend the ER for DMV biogenesis. Genome-wide screens revealed the autophagy proteins VMP1 and TMEM41B as important host factors for SARS-CoV-2 infection. Here, we demonstrated that DMV biogenesis, induced by virus infection or expression of nsp3/4, is impaired in the VMP1 KO or TMEM41B KO cells. In VMP1 KO cells, the nsp3/4 complex forms normally, but the zippered ER fails to close into DMVs. In TMEM41B KO cells, the nsp3–nsp4 interaction is reduced and DMV formation is suppressed. Thus, VMP1 and TMEM41B function at different steps during DMV formation. VMP1 was shown to regulate cross-membrane phosphatidylserine (PS) distribution. Inhibiting PS synthesis partially rescues the DMV defects in VMP1 KO cells, suggesting that PS participates in DMV formation. We provide molecular insights into the collaboration of host factors with viral proteins to remodel host organelles. Rockefeller University Press 2022-05-10 /pmc/articles/PMC9097365/ /pubmed/35536318 http://dx.doi.org/10.1083/jcb.202112081 Text en © 2022 Ji et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Report
Ji, Mingming
Li, Meng
Sun, Long
Zhao, Hongyu
Li, Ying
Zhou, Lulu
Yang, Zhenni
Zhao, Xin
Qu, Wenyan
Xue, Hanbing
Zheng, Ze
Li, Yiming
Deng, Hongyu
Zhao, Yan G.
VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection
title VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection
title_full VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection
title_fullStr VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection
title_full_unstemmed VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection
title_short VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection
title_sort vmp1 and tmem41b are essential for dmv formation during β-coronavirus infection
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097365/
https://www.ncbi.nlm.nih.gov/pubmed/35536318
http://dx.doi.org/10.1083/jcb.202112081
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