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Seneca Valley virus circumvents Gasdermin A-mediated inflammation by targeting the pore-formation domain for cleavage.

Hongyan YinZhenchao ZhaoYa YanYe YuanWeiyu QuHaiwei WangCheng ZhuPingwei LiXin Li
Published in: mBio (2024)
, which initiates pyroptosis. However, it is not clear if viral proteases also cleave GSDMA. In this study, we show that a fragment of porcine GSDMA (pGSDMA) containing the first 252 residues constitutes the pore-forming domain responsible for inducing lytic cell death and pyroptosis. Interestingly, picornavirus Seneca Valley Virus (SVV) protease 3C cleaves both pGSDMA and hGSDMA, generating a shorter fragment that fails to associate with the plasma membrane and does not induce pyroptosis. This cleavage by SVV 3C suppresses GSDMA-mediated lactate dehydrogenase release, bactericidal activity, and lytic cell death. This study reveals how SVV subverts host inflammatory defense by disrupting GSDMA-induced pyroptosis, thereby advancing our understanding of antiviral immunity and opening avenues for treating GSDMA-associated autoimmune diseases.
Keyphrases
  • cell death
  • nlrp inflammasome
  • oxidative stress
  • sars cov
  • signaling pathway
  • dna binding
  • high glucose
  • cell proliferation
  • endothelial cells
  • drug induced