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SARS-CoV-2 Nonstructural Proteins 1 and 13 Suppress Caspase-1 and the NLRP3 Inflammasome Activation

Na-Eun Kim1, Dae-Kyum Kim2,3,4,5, Yoon-Jae Song1

  • 1Department of Life Science, Gachon University, Seongnam-Si, Gyeonggi-do 13120, Korea.

Microorganisms
|March 3, 2021
PubMed

Insights

SARS-CoV-2 nonstructural proteins (NSPs) NSP1 and NSP13 antagonize the NLRP3 inflammasome. These viral proteins inhibit caspase-1 activation and IL-1β secretion, crucial for antiviral defense.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Inflammasome activation by viral infections has dual effects on hosts.
  • Dysregulated inflammasome activation contributes to disease severity in coronavirus infections.
  • Coronaviruses encode proteins that modulate inflammasome activity.

Purpose of the Study:

  • To investigate the role of SARS-CoV-2 nonstructural proteins (NSPs) in inflammasome activation.
  • To identify specific SARS-CoV-2 proteins that antagonize the NLRP3 inflammasome pathway.
  • To elucidate the mechanisms by which SARS-CoV-2 evades inflammasome-mediated immunity.

Main Methods:

  • Screening of a SARS-CoV-2 complementary DNA (cDNA) library encoding 28 open reading frames (ORFs).
  • Assessing the inhibition of caspase-1-mediated IL-1β activation by viral proteins.
  • Evaluating the effect of NSPs on NLRP3-inflammasome-induced caspase-1 activity and IL-1β secretion in THP-1 cells.

Main Results:

  • Two SARS-CoV-2 NSPs, NSP1 and NSP13, were identified as inhibitors of caspase-1-mediated IL-1β activation.
  • NSP1's host translation shutoff function and NSP13's helicase activity were associated with caspase-1 inhibition.
  • Both NSP1 and NSP13 significantly reduced NLRP3-inflammasome-induced caspase-1 activity and IL-1β secretion.

Conclusions:

  • SARS-CoV-2 NSP1 and NSP13 act as potent antagonists of the NLRP3 inflammasome.
  • These viral proteins play a role in SARS-CoV-2's evasion of host antiviral immune responses.
  • Understanding these interactions is crucial for comprehending coronavirus pathogenesis.
Keywords:
caspase-1inflammasomenonstructural proteinsevere acute respiratory syndrome coronavirus 2

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