tetano
Editor, Senior Moderator
PLoS One
. 2024 Apr 25;19(4):e0302436.
doi: 10.1371/journal.pone.0302436. eCollection 2024. Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC
Germán Ricardo Magaña-Ávila[SUP] 1 2 [/SUP], Erika Moreno[SUP] 1 [/SUP], Consuelo Plata[SUP] 1 [/SUP], Héctor Carbajal-Contreras[SUP] 1 3 [/SUP], Adrian Rafael Murillo-de-Ozores[SUP] 1 2 [/SUP], Kevin García-Ávila[SUP] 1 [/SUP], Norma Vázquez[SUP] 4 [/SUP], Maria Syed[SUP] 5 [/SUP], Jan Wysocki[SUP] 5 [/SUP], Daniel Batlle[SUP] 5 [/SUP], Gerardo Gamba[SUP] 1 3 4 [/SUP], María Castañeda-Bueno[SUP] 1 [/SUP]
Affiliations
Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na+ reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of αENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and αENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between 〈ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining.
. 2024 Apr 25;19(4):e0302436.
doi: 10.1371/journal.pone.0302436. eCollection 2024. Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC
Germán Ricardo Magaña-Ávila[SUP] 1 2 [/SUP], Erika Moreno[SUP] 1 [/SUP], Consuelo Plata[SUP] 1 [/SUP], Héctor Carbajal-Contreras[SUP] 1 3 [/SUP], Adrian Rafael Murillo-de-Ozores[SUP] 1 2 [/SUP], Kevin García-Ávila[SUP] 1 [/SUP], Norma Vázquez[SUP] 4 [/SUP], Maria Syed[SUP] 5 [/SUP], Jan Wysocki[SUP] 5 [/SUP], Daniel Batlle[SUP] 5 [/SUP], Gerardo Gamba[SUP] 1 3 4 [/SUP], María Castañeda-Bueno[SUP] 1 [/SUP]
Affiliations
- PMID: 38662786
- DOI: 10.1371/journal.pone.0302436
Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na+ reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of αENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and αENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between 〈ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining.