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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Virology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1473504

miR-191-5p Suppresses PRRSV Replication by Targeting Porcine EGFR to Enhance Interferon Signaling

Provisionally accepted
Yu Pan Yu Pan 1Lin Zhang Lin Zhang 1Wenjie Ma Wenjie Ma 1Yassein Ibrahim Yassein Ibrahim 2Wenli Zhang Wenli Zhang 1Mengjie Wang Mengjie Wang 1Xinrong Wang Xinrong Wang 3Yunfei Xu Yunfei Xu 1Caixia Gao Caixia Gao 1Hongyan Chen Hongyan Chen 1He Zhang He Zhang 1Changyou Xia Changyou Xia 1Yue WANG Yue WANG 1,2,3*
  • 1 Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang Province, China
  • 2 Chongqing Key Laboratory of Pig Industry Sciences, Chongqing Academy of Animal Science, Chongqing, China
  • 3 College of Veterinary Medicine, Southwest University, Chongqing, China

The final, formatted version of the article will be published soon.

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major thread to the global swine industry, lack of effective control strategies. This study explores the regulatory role of a small non-coding RNA, miR-191-5p, in PRRSV infection. We observed that miR-191-5p significantly inhibits PRRSV in porcine alveolar macrophages (PAMs), contrasting with negligible effects in MARC-145 and HEK293-CD163 cells, suggesting a cell-specific antiviral effect. Further investigation unveiled that miR-191-5p directly targets the porcine epidermal growth factor receptor (EGFR), whose overexpression or EGF-induced activation suppresses type I interferon (IFN-I) signaling, promoting PRRSV replication. In contrast, siRNA-or miR-191-5p-induced EGFR downregulation or EGFR inhibitor boosts IFN-I signaling, reducing viral replication. Notably, this miRNA alleviates the suppressive effect of EGF on IFN-I signaling, underscoring its regulatory function. Further investigation revealed interconnections among miR-191-5p, EGFR and signal transducer and activator of transcription 3 (STAT3). Modulation of STAT3 activity influenced IFN-I signaling and PRRSV replication, with STAT3 knockdown countering EGFR activation-induced virus replication. Combination inhibition of STAT3 and miR-191-5p suggests that STAT3 acts downstream in EGFR's antiviral response. Furthermore, miR-191-5p's broad efficacy in restricting various PRRSV strains in PAMs was identified. Collectively, these findings elucidate a novel mechanism of miR-191-5p in activating host IFN-I signaling to inhibit PRRSV replication, highlighting its potential in therapeutic applications against PRRSV.

    Keywords: Porcine Reproductive and Respiratory Syndrome Virus, miR-191-5p, porcine epidermal growth factor receptor, Signal transducer and activator of transcription 3, IFN-I

    Received: 31 Jul 2024; Accepted: 04 Oct 2024.

    Copyright: © 2024 Pan, Zhang, Ma, Ibrahim, Zhang, Wang, Wang, Xu, Gao, Chen, Zhang, Xia and WANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yue WANG, College of Veterinary Medicine, Southwest University, Chongqing, China

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