کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6138976 | 1594232 | 2015 | 10 صفحه PDF | دانلود رایگان |
- 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.
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: Virology - Volume 485, November 2015, Pages 330-339