Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome.
Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein-lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Jose L
JL
Nieto-Torres
Department of Physics, Laboratory of Molecular Biophysics. Universitat Jaume I, 12071 Castellón, Spain.
Carmina
C
Verdiá-Báguena
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Jose M
JM
Jimenez-Guardeño
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Jose A
JA
Regla-Nava
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Carlos
C
Castaño-Rodriguez
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Raul
R
Fernandez-Delgado
School of Biological Sciences, Division of Structural and Computational Biology, Nanyang Technological University, Singapore 637551, Singapore.
Jaume
J
Torres
Department of Physics, Laboratory of Molecular Biophysics. Universitat Jaume I, 12071 Castellón, Spain. Electronic address: aguilell@uji.es.
Vicente M
VM
Aguilella
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain. Electronic address: L.Enjuanes@cnb.csic.es.
Luis
L
Enjuanes
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D058847:Inflammasomes / Q000378:metabolism*; D007477:Ions / Q000378:metabolism*; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism / Q000821:virology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
D015220:Calcium Channels; D002352:Carrier Proteins; C501689:E protein, SARS coronavirus; D058847:Inflammasomes; D007477:Ions; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D014759:Viral Envelope Proteins; D000086082:Viroporin Proteins; D002118:Calcium
Calcium; Coronavirus; E protein; Inflammasome; Ion channel; Pathogenesis; SARS-CoV; Viroporin