Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome

Abstract 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 th...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2015-11, Vol.485, p.330-339
Main Authors: Nieto-Torres, Jose L, Verdiá-Báguena, Carmina, Jimenez-Guardeño, Jose M, Regla-Nava, Jose A, Castaño-Rodriguez, Carlos, Fernandez-Delgado, Raul, Torres, Jaume, Aguilella, Vicente M, Enjuanes, Luis
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Calcium
Calcium - metabolism
Calcium Channels - metabolism
Carrier Proteins - metabolism
Chlorocebus aethiops
Coronavirus
E protein
Infectious Disease
Inflammasome
Inflammasomes - metabolism
Ion channel
Ions - metabolism
Mutation
NLR Family, Pyrin Domain-Containing 3 Protein
Pathogenesis
SARS Virus - genetics
SARS Virus - metabolism
SARS-CoV
Severe Acute Respiratory Syndrome - metabolism
Severe Acute Respiratory Syndrome - virology
Vero Cells
Viral Envelope Proteins - genetics
Viral Envelope Proteins - metabolism
Viroporin
Viroporin Proteins
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Summary:Abstract 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2015.08.010