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Article

Disruption of the Golgi Apparatus and Contribution of the Endoplasmic Reticulum to the SARS-CoV-2 Replication Complex

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Host-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
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Innate Immunity and Pathogenesis Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
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Microscopy Unit, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
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Molecular Pathogenesis Unit, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
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Coxiella Pathogenesis Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Andrew Davidson and Stephen P. Goff
Viruses 2021, 13(9), 1798; https://doi.org/10.3390/v13091798
Received: 30 July 2021 / Revised: 12 August 2021 / Accepted: 31 August 2021 / Published: 9 September 2021
(This article belongs to the Section SARS-CoV-2 and COVID-19)
A variety of immunolabeling procedures for both light and electron microscopy were used to examine the cellular origins of the host membranes supporting the SARS-CoV-2 replication complex. The endoplasmic reticulum has long been implicated as a source of membrane for the coronavirus replication organelle. Using dsRNA as a marker for sites of viral RNA synthesis, we provide additional evidence supporting ER as a prominent source of membrane. In addition, we observed a rapid fragmentation of the Golgi apparatus which is visible by 6 h and complete by 12 h post-infection. Golgi derived lipid appears to be incorporated into the replication organelle although protein markers are dispersed throughout the infected cell. The mechanism of Golgi disruption is undefined, but chemical disruption of the Golgi apparatus by brefeldin A is inhibitory to viral replication. A search for an individual SARS-CoV-2 protein responsible for this activity identified at least five viral proteins, M, S, E, Orf6, and nsp3, that induced Golgi fragmentation when expressed in eukaryotic cells. Each of these proteins, as well as nsp4, also caused visible changes to ER structure as shown by correlative light and electron microscopy (CLEM). Collectively, these results imply that specific disruption of the Golgi apparatus is a critical component of coronavirus replication. View Full-Text
Keywords: SARS-CoV-2; cell biology; microscopy; electron microscopy; Golgi; ER SARS-CoV-2; cell biology; microscopy; electron microscopy; Golgi; ER
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MDPI and ACS Style

Hackstadt, T.; Chiramel, A.I.; Hoyt, F.H.; Williamson, B.N.; Dooley, C.A.; Beare, P.A.; de Wit, E.; Best, S.M.; Fischer, E.R. Disruption of the Golgi Apparatus and Contribution of the Endoplasmic Reticulum to the SARS-CoV-2 Replication Complex. Viruses 2021, 13, 1798. https://doi.org/10.3390/v13091798

AMA Style

Hackstadt T, Chiramel AI, Hoyt FH, Williamson BN, Dooley CA, Beare PA, de Wit E, Best SM, Fischer ER. Disruption of the Golgi Apparatus and Contribution of the Endoplasmic Reticulum to the SARS-CoV-2 Replication Complex. Viruses. 2021; 13(9):1798. https://doi.org/10.3390/v13091798

Chicago/Turabian Style

Hackstadt, Ted, Abhilash I. Chiramel, Forrest H. Hoyt, Brandi N. Williamson, Cheryl A. Dooley, Paul A. Beare, Emmie de Wit, Sonja M. Best, and Elizabeth R. Fischer 2021. "Disruption of the Golgi Apparatus and Contribution of the Endoplasmic Reticulum to the SARS-CoV-2 Replication Complex" Viruses 13, no. 9: 1798. https://doi.org/10.3390/v13091798

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