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

Virology. 2015 Nov;485:330-9. doi: 10.1016/j.virol.2015.08.010. Epub 2015 Aug 29.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Carrier Proteins / metabolism*
  • Chlorocebus aethiops
  • Inflammasomes / metabolism*
  • Ions / metabolism*
  • Mutation
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • SARS Virus / genetics
  • SARS Virus / metabolism*
  • Severe Acute Respiratory Syndrome / metabolism
  • Severe Acute Respiratory Syndrome / virology
  • Vero Cells
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Viroporin Proteins

Substances

  • Calcium Channels
  • Carrier Proteins
  • E protein, SARS coronavirus
  • Inflammasomes
  • Ions
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Viral Envelope Proteins
  • Viroporin Proteins
  • Calcium