NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response.
Xingyu LiGuangde ZhouXingzi SunSiying QuHongzhi LaiYongjian WuDechang LiLei LiuGuoliang ZhangJingwen YangXi HuangPublished in: The Journal of infectious diseases (2023)
COVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat-containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed that NLRP12 directly interacted with the M protein through its leucine-rich repeat domain. Moreover, in vitro studies demonstrated that NLRP12 interacted with TRAF3 and promoted its ubiquitination and degradation, which counteracted the inhibitory effect of TRAF3 on the NF-κB/MAPK signaling pathway and promoted the production of inflammatory cytokines. Furthermore, an in vivo study revealed that NLRP12 knockout mice displayed attenuated tissue injury and ameliorated inflammatory responses in the lungs when infected with a SARS-CoV-2 M protein-reconstituted pseudovirus and mouse coronavirus. Taken together, these findings suggest that NLRP12 mediates the inflammatory responses during coronavirus infection.
Keyphrases
- sars cov
- signaling pathway
- respiratory syndrome coronavirus
- nlrp inflammasome
- inflammatory response
- pi k akt
- oxidative stress
- endothelial cells
- poor prognosis
- single cell
- protein protein
- liver failure
- physical activity
- induced apoptosis
- lipopolysaccharide induced
- peripheral blood
- small molecule
- hepatitis b virus
- cell proliferation
- emergency department
- high density
- dna binding
- drug induced
- weight gain
- nuclear factor
- endoplasmic reticulum stress