Identification of host dependency factors involved in SARS-CoV-2 replication organelle formation through proteomics and ultrastructural analysis

Remodeling of the cellular endomembrane system by viruses allows for efficient and coordinated replication of the viral genome in distinct subcellular compartments termed replication organelles. As a critical step in the viral life cycle, replication organelle formation is an attractive target for t...

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Published inJournal of virology Vol. 97; no. 11; p. e0087823
Main Authors Pahmeier, Felix, Lavacca, Teresa-Maria, Goellner, Sarah, Neufeldt, Christopher J, Prasad, Vibhu, Cerikan, Berati, Rajasekharan, Sreejith, Mizzon, Giulia, Haselmann, Uta, Funaya, Charlotta, Scaturro, Pietro, Cortese, Mirko, Bartenschlager, Ralf
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 30.11.2023
Subjects
COVID-19
Humans
Organelles - metabolism
Proteomics
SARS-CoV-2 - physiology
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Virus Replication
Virus-Cell Interactions
coronavirus
host-pathogen interactions
double-membrane vesicle
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Summary:Remodeling of the cellular endomembrane system by viruses allows for efficient and coordinated replication of the viral genome in distinct subcellular compartments termed replication organelles. As a critical step in the viral life cycle, replication organelle formation is an attractive target for therapeutic intervention, but factors central to this process are only partially understood. In this study, we corroborate that two viral proteins, nsp3 and nsp4, are the major drivers of membrane remodeling in SARS-CoV-2 infection. We further report a number of host cell factors interacting with these viral proteins and supporting the viral replication cycle, some of them by contributing to the formation of the SARS-CoV-2 replication organelle.
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Felix Pahmeier and Teresa-Maria Lavacca contributed equally to this article. The order of authorship corresponds to the chronological order in which the authors were involved in the project.
Present address: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA
Present address: Cell Biology and Disease Mechanisms, Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
The authors declare no conflict of interest.
Present address: Department of Cells, Seeds and Research, UniQure B.V., Amsterdam, Netherlands
ISSN:0022-538X
1098-5514
1098-5514
DOI:10.1128/jvi.00878-23