Elsevier

Virology

Volume 485, November 2015, Pages 330-339
Virology

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

https://doi.org/10.1016/j.virol.2015.08.010Get rights and content
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Highlights

  • SARS-CoV E protein forms calcium ion channels, a novel highly relevant function.

  • Transport of calcium ions through E protein channel stimulates the inflammasome.

  • Inflammasome derived exacerbated proinflammation causes SARS worsening.

  • E protein ion channel and its driven proinflammation may be targets to treat SARS.

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.

Keywords

SARS-CoV
Coronavirus
E protein
Ion channel
Viroporin
Calcium
Inflammasome
Pathogenesis

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1

Both authors equally contributed to this work.