FADD promotes type I interferon production to suppress porcine reproductive and respiratory syndrome virus infection

Xiaobo Chang; Mengqi Wang; Zhaopeng Li; Lei Wang; Gaiping Zhang; Yafei Chang; Jianhe Hu

doi:10.3389/fvets.2024.1380144

FADD promotes type I interferon production to suppress porcine reproductive and respiratory syndrome virus infection

Front Vet Sci. 2024 Apr 8:11:1380144. doi: 10.3389/fvets.2024.1380144. eCollection 2024.

Authors

Xiaobo Chang^{1

2}, Mengqi Wang², Zhaopeng Li², Lei Wang², Gaiping Zhang³, Yafei Chang^{1

2}, Jianhe Hu^{1

2}

Affiliations

¹ Postdoctoral Innovation Practice Base, College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
² College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
³ College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide, causing huge economic losses to the global swine industry. Fas-associated death domain (FADD) was previously reported to be an adaptor protein that functions in transferring the apoptotic signals regulated by the death receptors. In the current study, we unravel its unidentified role in promoting type I interferon (IFN) production during PRRS virus (PRRSV) infection. We identified that FADD inhibited PRRSV infection via promotion of type I IFN transcription. Overexpression of FADD suppressed the replication of PRRSV, while knockout of FADD increased viral titer and nucleocapsid protein expression. Mechanistically, FADD promoted mitochondrial antiviral signaling protein (MAVS)-mediated production of IFN-β and some IFN-stimulated genes (ISGs). Furthermore, FADD exerted anti-PRRSV effects in a MAVS-dependent manner and increased the type I IFN signaling during PRRSV infection. This study highlights the importance of FADD in PRRSV replication, which may have implications for the future control of PRRS.

Keywords: FADD; MAVS; PRRSV; antiviral response; type I IFN signaling.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The research was supported by the Youth Fund of the Natural Science Foundation of Henan Province (222300420157), the Henan Provincial Science and Technology Research Project (222102110387), the National Natural Science Foundation of China (32172862), the Outstanding Youth Foundation of Henan Scientific Committee (222300420043), and the Leading Talents of Scientific and Technological Innovation in the Central Plains (224200510024).