Journal
VIROLOGY
Volume 485, Issue -, Pages 330-339Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2015.08.010
Keywords
SARS-CoV; Coronavirus; E protein; Ion channel; Viroporin; Calcium; Inflammasome; Pathogenesis
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Funding
- Government of Spain [BIO2013-42869-R, FIS2013-40473-P]
- Generalitat Valenciana [2012/069]
- Fundacio Caixa Castello-Bancaixa [P1-1B2012-03]
- U.S. National Institutes of Health (NIH) [5P01 AI060699]
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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-1 beta 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-1 beta 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. (C) 2015 Elsevier Inc. All rights reserved.
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