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SARS-CoV-2 nucleocapsid protein adheres to replication organelles before viral assembly at the Golgi/ERGIC and lysosome-mediated egress

Published version
Peer-reviewed

Type

Article

Change log

Authors

Mascheroni, Luca 
Wunderlich, Lucia 
Makarchuk, Stanislaw  ORCID logo  https://orcid.org/0000-0001-5484-7141

Abstract

Despite being the target of extensive research efforts due to the COVID-19 pandemic, relatively little is known about the dynamics of SARS-CoV-2 replication within cells. We investigate and characterise the tightly orchestrated sequence of events during different stages of the infection cycle by visualising the spatiotemporal dynamics of the four structural proteins of SARS-CoV-2 at high resolution. The nucleoprotein is expressed first and accumulates around folded ER membranes in convoluted layers that connect to viral RNA replication foci. We find that of the three transmembrane proteins, the membrane protein appears at the Golgi apparatus/ERGIC before the spike and envelope proteins. Relocation of the lysosome marker LAMP1 towards the assembly compartment and its detection in transport vesicles of viral proteins confirm an important role of lysosomes in SARS-CoV-2 egress. These data provide new insights into the spatiotemporal regulation of SARS-CoV-2 assembly, and refine current understanding of SARS-CoV-2 replication.

Description

Keywords

3101 Biochemistry and Cell Biology, 3102 Bioinformatics and Computational Biology, 31 Biological Sciences, Coronaviruses, Coronaviruses Therapeutics and Interventions, Emerging Infectious Diseases, Infectious Diseases, 2.2 Factors relating to the physical environment, Infection, 3 Good Health and Well Being

Journal Title

Science Advances

Conference Name

Journal ISSN

2375-2548
2375-2548

Volume Title

Publisher

American Association for the Advancement of Science
Sponsorship
Engineering and Physical Sciences Research Council (EP/H018301/1)
Wellcome Trust (089703/Z/09/Z)
Medical Research Council (MR/K015850/1)
Medical Research Council (MR/K02292X/1)
Engineering and Physical Sciences Research Council (EP/L015889/1)
Medical Research Council (G0902243)
Wellcome Trust (203249/Z/16/Z)
AstraZeneca; Infinitus (China) Ltd.
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