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 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.

journal_name

Virology

journal_title

Virology

authors

Nieto-Torres JL,Verdiá-Báguena C,Jimenez-Guardeño JM,Regla-Nava JA,Castaño-Rodriguez C,Fernandez-Delgado R,Torres J,Aguilella VM,Enjuanes L

doi

10.1016/j.virol.2015.08.010

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

330-9

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(15)00356-6

journal_volume

485

pub_type

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