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Swine Influenza Virus Induces RIPK1/DRP1-Mediated Interleukin-1 Beta Production

by Hong-Su Park 1,2, Guanqun Liu 1,3, Qiang Liu 1,2,3 and Yan Zhou 1,2,3,*
1
Vaccine and Infectious Disease Organization—International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
2
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
3
Vaccinology and Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada
*
Author to whom correspondence should be addressed.
Viruses 2018, 10(8), 419; https://doi.org/10.3390/v10080419
Received: 16 July 2018 / Revised: 4 August 2018 / Accepted: 6 August 2018 / Published: 9 August 2018
(This article belongs to the Section Animal Viruses)
Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome plays a pivotal role in modulating lung inflammation in response to the influenza A virus infection. We previously showed that the swine influenza virus (SIV) infection induced NLRP3 inflammasome-mediated IL-1β production in primary porcine alveolar macrophages (PAMs), and we were interested in examining the upstream signaling events that are involved in this process. Here, we report that the SIV-infection led to dynamin-related protein 1 (DRP1) phosphorylation at serine 579 and mitochondrial fission in PAMs. IL-1β production was dependent on the reactive oxygen species (ROS) production, and DRP1 phosphorylation resulted in the upregulation of the NLRP3 inflammasome. Furthermore, the requirement of the kinase activity of receptor-interacting protein kinase 1 (RIPK1) for the IL-1β production and RIPK1-DRP1 association suggested that RIPK1 is an upstream kinase for DRP1 phosphorylation. Our results reveal a critical role of the RIPK1/DRP1 signaling axis, whose activation leads to mitochondrial fission and ROS release, in modulating porcine NLRP3 inflammasome-mediated IL-1β production in SIV-infected PAMs. View Full-Text
Keywords: swine influenza virus; interleukin-1 beta; NLRP3 inflammasome; receptor-interacting protein kinase 1; dynamin-related protein 1; mitochondrial fission; porcine alveolar macrophage swine influenza virus; interleukin-1 beta; NLRP3 inflammasome; receptor-interacting protein kinase 1; dynamin-related protein 1; mitochondrial fission; porcine alveolar macrophage
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MDPI and ACS Style

Park, H.-S.; Liu, G.; Liu, Q.; Zhou, Y. Swine Influenza Virus Induces RIPK1/DRP1-Mediated Interleukin-1 Beta Production. Viruses 2018, 10, 419.

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