SARS-CoV-2 targets the lysosome to mediate airway inflammatory cell death.

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic continues to wreak havoc, researchers around the globe are working together to understand how the responsible agent - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) damages the respiratory system and other organs. Macroautophagy/autophagy is an innate immune response against viral infection and is known to be manipulated by positive-strand RNA viruses, including SARS-CoV-2. Nevertheless, the link between autophagic subversion and cell death or inflammation in COVID-19 remains unclear. Emerging evidence suggests that SARS-CoV-2 could trigger pyroptosis, a form of inflammatory programmed cell death characterized by the activation of inflammasomes and CASP1 (caspase 1) and the formation of transmembrane pores by GSDMD (gasdermin D). In this connection, autophagic flux impairment is a known activator of inflammasomes. This prompted us to investigate if SARS-CoV-2 could target autophagy to induce inflammasome-dependent pyroptosis in lung epithelial cells.Abbreviations ATP6AP1 ATPase H+ transporting accessory protein 1; CASP1 caspase 1; COVID-19 coronavirus disease 2019; GSDMD gasdermin D; IL1B interleukin 1 beta; IL18 interleukin 18; KRT 18 keratin 18; NLRP3 NLR family pyrin domain containing 3; NOD nucleotide oligomerization domain; NSP6 non-structural protein 6; TFEB transcription factor EB; SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.