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

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Mascheroni, Luca 
Wunderlich, Lucia 
Makarchuk, Stanislaw  ORCID logo

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.

3101 Biochemistry and Cell Biology, 3102 Bioinformatics and Computational Biology, 31 Biological Sciences, Prevention, Lung, Vaccine Related, Pneumonia, Infectious Diseases, Emerging Infectious Diseases, Biodefense, Pneumonia & Influenza, Infection, Generic health relevance, 3 Good Health and Well Being
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Science Advances
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American Association for the Advancement of Science
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)
AstraZeneca; Infinitus (China) Ltd.
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