Portal de Periódicos da CAPES

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

2015; Elsevier BV; Volume: 485; Linguagem: Inglês

10.1016/j.virol.2015.08.010

1096-0341

José L. Nieto-Torres, Carmina Verdiá-Báguena, Jose M. Jiménez-Guardeño, José Ángel Regla-Nava, Carlos Castaño-Rodríguez, Raúl Fernández‐Delgado, Jaume Torres, Vicente M. Aguilella, Luis Enjuanes,

Inflammasome and immune disorders

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.