SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.

The COVID-19 pandemic is caused by the enveloped virus SARS-CoV-2. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic G...

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Main Authors: Jianchao Zhang, Andrew Kennedy, Daniel Macedo de Melo Jorge, Lijuan Xing, Whitney Reid, Sarah Bui, Joseph Joppich, Molly Rose, Sevval Ercan, Qiyi Tang, David Ginsburg, Andrew W Tai, Yanzhuang Wang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-06-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1013295
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author Jianchao Zhang
Andrew Kennedy
Daniel Macedo de Melo Jorge
Lijuan Xing
Whitney Reid
Sarah Bui
Joseph Joppich
Molly Rose
Sevval Ercan
Qiyi Tang
David Ginsburg
Andrew W Tai
Yanzhuang Wang
author_facet Jianchao Zhang
Andrew Kennedy
Daniel Macedo de Melo Jorge
Lijuan Xing
Whitney Reid
Sarah Bui
Joseph Joppich
Molly Rose
Sevval Ercan
Qiyi Tang
David Ginsburg
Andrew W Tai
Yanzhuang Wang
author_sort Jianchao Zhang
collection DOAJ
description The COVID-19 pandemic is caused by the enveloped virus SARS-CoV-2. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation. SARS-CoV-2 virions are enriched in the fragmented Golgi. Blocking endoplasmic reticulum (ER) to Golgi trafficking dramatically inhibits SARS-CoV-2 assembly and secretion without reducing viral genome replication. Significantly, SARS-CoV-2 infection down-regulates GRASP55 but up-regulates TGN46 protein levels. Surprisingly, GRASP55 expression reduces both viral secretion and spike number on each virion without affecting viral entry, while GRASP55 depletion displays opposite effects. In contrast, TGN46 depletion only inhibits viral secretion without affecting spike incorporation into virions. Taken together, we show that SARS-CoV-2 alters Golgi structure and function to modulate viral assembly and secretion, highlighting the Golgi as a potential therapeutic target for blocking SARS-CoV-2 infection.
format Article
id doaj-art-845f8a5fa47c429bb5e3947f09959b4b
institution Kabale University
issn 1553-7366
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language English
publishDate 2025-06-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Pathogens
spelling doaj-art-845f8a5fa47c429bb5e3947f09959b4b2025-08-20T03:50:07ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-06-01216e101329510.1371/journal.ppat.1013295SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.Jianchao ZhangAndrew KennedyDaniel Macedo de Melo JorgeLijuan XingWhitney ReidSarah BuiJoseph JoppichMolly RoseSevval ErcanQiyi TangDavid GinsburgAndrew W TaiYanzhuang WangThe COVID-19 pandemic is caused by the enveloped virus SARS-CoV-2. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation. SARS-CoV-2 virions are enriched in the fragmented Golgi. Blocking endoplasmic reticulum (ER) to Golgi trafficking dramatically inhibits SARS-CoV-2 assembly and secretion without reducing viral genome replication. Significantly, SARS-CoV-2 infection down-regulates GRASP55 but up-regulates TGN46 protein levels. Surprisingly, GRASP55 expression reduces both viral secretion and spike number on each virion without affecting viral entry, while GRASP55 depletion displays opposite effects. In contrast, TGN46 depletion only inhibits viral secretion without affecting spike incorporation into virions. Taken together, we show that SARS-CoV-2 alters Golgi structure and function to modulate viral assembly and secretion, highlighting the Golgi as a potential therapeutic target for blocking SARS-CoV-2 infection.https://doi.org/10.1371/journal.ppat.1013295
spellingShingle Jianchao Zhang
Andrew Kennedy
Daniel Macedo de Melo Jorge
Lijuan Xing
Whitney Reid
Sarah Bui
Joseph Joppich
Molly Rose
Sevval Ercan
Qiyi Tang
David Ginsburg
Andrew W Tai
Yanzhuang Wang
SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.
PLoS Pathogens
title SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.
title_full SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.
title_fullStr SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.
title_full_unstemmed SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.
title_short SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.
title_sort sars cov 2 remodels the golgi apparatus to facilitate viral assembly and secretion
url https://doi.org/10.1371/journal.ppat.1013295
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