Stimulation of PSTPIP1 to trigger proinflammatory responses in asymptomatic SARS-CoV-2 infections.

ABSTRACT

Background: A hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection gravely worsens the clinical progression of coronavirus disease 2019 (COVID-19). Although the undesirable effects of inflammasome activation have been correlated to the severity of COVID-19, the mechanisms of this process in the asymptomatic infection and disease progression have not yet been clearly elucidated. Methods: We performed strand-specific RNA sequencing in 39 peripheral blood mononuclear cell (PBMC) samples from asymptomatic individuals（n = 10）, symptomatic patients（n = 16） and healthy donors（n = 13）. Results: Dysregulation of pyrin inflammasomes along with the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene was identified in SARS-COV-2 infection. Notably, the PSTPIP1 expression level showed a significant negative correlation with an adjacent long-noncoding RNA (lncRNA) RP11-797A18.6 in the asymptomatic individuals compared with the healthy controls. In addition, a decline in the nuclear factor kappa B subunit 1 (NFKB1) gene expression was observed in asymptomatic infection, followed by a rise in the mild and moderate disease stages, suggesting that altered NFKB1 expression and associated proinflammatory signals may trigger a disease progression. Conclusions: Overall, our results indicate that PSTPIP1-dependent pyrin inflammasomes-mediated pyroptosis and NF-κB activation might be potential preventive targets for COVID-19 disease development and progression.