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Viruses 2018, 10(8), 419; https://doi.org/10.3390/v10080419

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

1,2
,
1,3
,
1,2,3
and
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.
Received: 16 July 2018 / Revised: 4 August 2018 / Accepted: 6 August 2018 / Published: 9 August 2018
(This article belongs to the Section Animal Viruses)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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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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