Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication.
Coronaviruses (CoV), including SARS and mouse hepatitis virus (MHV), are enveloped RNA viruses that induce formation of double-membrane vesicles (DMVs) and target their replication and transcription complexes (RTCs) on the DMV-limiting membranes. The DMV biogenesis has been connected with the early secretory pathway. CoV-induced DMVs, however, lack conventional endoplasmic reticulum (ER) or Golgi protein markers, leaving their membrane origins in question. We show that MHV co-opts the host cell machinery for COPII-independent vesicular ER export of a short-living regulator of ER-associated degradation (ERAD), EDEM1, to derive cellular membranes for replication. MHV infection causes accumulation of EDEM1 and OS-9, another short-living ER chaperone, in the DMVs. DMVs are coated with the nonlipidated LC3/Atg8 autophagy marker. Downregulation of LC3, but not inactivation of host cell autophagy, protects cells from CoV infection. Our study identifies the host cellular pathway hijacked for supplying CoV replication membranes and describes an autophagy-independent role for nonlipidated LC3-I.
Reggiori
Fulvio
F
Department of Cell Biology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands. f.reggiori@umcutrecht.nl
Monastyrska
Iryna
I
Verheije
Monique H
MH
Calì
Tito
T
Ulasli
Mustafa
M
Bianchi
Siro
S
Bernasconi
Riccardo
R
de Haan
Cornelis A M
CA
Molinari
Maurizio
M
D000818:Animals; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000737:chemistry / Q000821:virology*; D004721:Endoplasmic Reticulum / Q000821:virology*; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D006517:Murine hepatitis virus / Q000502:physiology*; D014452:Ubiquitins / Q000032:analysis*; D014779:Virus Replication
C434526:Edem1 protein, mouse; C480859:Gabarapl1 protein, mouse; C480860:Map1lc3b protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D014452:Ubiquitins