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Open AccessArticle

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

1
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
2
Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China
3
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2019, 11(1), 39; https://doi.org/10.3390/v11010039
Received: 28 November 2018 / Revised: 27 December 2018 / Accepted: 2 January 2019 / Published: 9 January 2019
(This article belongs to the Special Issue MERS-CoV)
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection. View Full-Text
Keywords: MERS-CoV; inflammation; pyroptosis; complement MERS-CoV; inflammation; pyroptosis; complement
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Jiang, Y.; Li, J.; Teng, Y.; Sun, H.; Tian, G.; He, L.; Li, P.; Chen, Y.; Guo, Y.; Li, J.; Zhao, G.; Zhou, Y.; Sun, S. Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV. Viruses 2019, 11, 39.

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