title: Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4.
abstract: Coronaviruses replicate their genomes in association with rearranged cellular membranes. The coronavirus nonstructural integral membrane proteins (nsps) 3, 4 and 6, are key players in the formation of the rearranged membranes. Previously, we demonstrated that nsp3 and nsp4 interact and that their co-expression results in the relocalization of these proteins from the endoplasmic reticulum (ER) into discrete perinuclear foci. We now show that these foci correspond to areas of rearranged ER-derived membranes, which display increased membrane curvature. These structures, which were able to recruit other nsps, were only detected when nsp3 and nsp4 were derived from the same coronavirus species. We propose, based on the analysis of a large number of nsp3 and nsp4 mutants, that interaction between the large luminal loops of these proteins drives the formation of membrane rearrangements, onto which the coronavirus replication-transcription complexes assemble in infected cells.
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Marne C
authors.initials: MC
authors.lastname: Hagemeijer
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Iryna
authors.initials: I
authors.lastname: Monastyrska
authors.affiliation: Department of Cell Biology and Institute of Biomembranes, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Janice
authors.initials: J
authors.lastname: Griffith
authors.affiliation: Department of Cell Biology and Institute of Biomembranes, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Sluijs
authors.affiliation: Division of Cell Biology, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jarno
authors.initials: J
authors.lastname: Voortman
authors.affiliation: Division of Cell Biology, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands.
authors.forename: Paul M
authors.initials: PM
authors.lastname: van Bergen en Henegouwen
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Annelotte M
authors.initials: AM
authors.lastname: Vonk
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Rottier
authors.affiliation: Department of Cell Biology and Institute of Biomembranes, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands. Electronic address: c.a.m.dehaan@uu.nl.
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: de Haan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane; D017124:Conserved Sequence; D017934:Coronavirus / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000502:physiology / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D051379:Mice; D009154:Mutation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D017361:Viral Nonstructural Proteins
keywords: Coronavirus; Membrane rearrangements; Nsps; Replication–transcription complex; Transmembrane proteins