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Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV

Yuting Jiang1, Junfeng Li2, Yue Teng3

  • 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. captain99@126.com.

Viruses
|January 13, 2019
PubMed

Insights

Middle East respiratory syndrome coronavirus (MERS-CoV) infection triggers pyroptosis and complement overactivation in human cells and mice. Blocking the C5a-C5aR1 axis suppressed these inflammatory responses, offering new insights into MERS-CoV pathogenesis.

Area of Science:

  • Virology
  • Immunology
  • Pathogenesis

Background:

  • Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a significant mortality rate.
  • Previous studies established a human DPP4 transgenic (hDPP4-Tg) mouse model to investigate MERS-CoV immunopathogenesis.

Purpose of the Study:

  • To investigate the role of pyroptosis in MERS-CoV infection within THP-1 cells and hDPP4-Tg mice.
  • To elucidate the link between complement overactivation and pyroptosis during MERS-CoV infection.

Main Methods:

  • Infection of THP-1 cells and hDPP4-Tg mice with MERS-CoV.
  • Analysis of pyroptosis markers (caspase-1) and inflammatory cytokines (IL-1β).
  • Blocking the C5a-C5aR1 axis using an anti-C5aR1 antibody to assess its effect on MERS-CoV-induced inflammation.

Main Results:

  • MERS-CoV infection induced pyroptosis and complement overactivation in human macrophages.
  • hDPP4-Tg mice showed increased caspase-1 expression and IL-1β levels post-infection.
  • Inhibition of the C5a-C5aR1 axis significantly reduced caspase-1 and IL-1β levels, suppressing pyroptosis and inflammation.

Conclusions:

  • MERS-CoV infection leads to complement overactivation, potentially driving pyroptosis and inflammation.
  • Targeting the C5a-C5aR1 axis can suppress MERS-CoV-induced pyroptosis and inflammation.
  • These findings enhance understanding of MERS-CoV pathogenesis and suggest potential therapeutic targets.
Keywords:
MERS-CoVcomplementinflammationpyroptosis

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