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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Veterinary and Zoonotic Infection
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1431836
This article is part of the Research Topic Exploring Zoonoses: Therapeutic Strategies and Drug Mechanisms View all articles

Melatonin Inhibits Bovine Viral Diarrhea Virus Replication by ER Stress-Mediated NF-κB Signal Pathway and Autophagy in MDBK Cells

Provisionally accepted
Yi-Qing Zhao Yi-Qing Zhao 1Xue-Fei Wang Xue-Fei Wang 1*Jia-Lu Zhang Jia-Lu Zhang 1*Yi Wu Yi Wu 1*Jing Wang Jing Wang 2*Jiufeng Wang Jiufeng Wang 1*
  • 1 China Agricultural University, Beijing, China
  • 2 Zhejiang Agriculture and Forestry University, Hangzhou, Zhejiang Province, China

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

    Bovine viral diarrhea-mucosal disease (BVD-MD) is a contagious disease in cattle, caused by the bovine viral diarrhea virus (BVDV). This virus continues to spread globally, exerting pressure on both public health and the economy. Despite its impact, there are currently no effective drugs for treating BVDV. This study utilized Madin-Darby bovine kidney (MDBK) cells as a model to investigate the antiviral effects of melatonin against Bovine Viral Diarrhea Virus (BVDV) and its connection with endoplasmic reticulum (ER) stress. Our results show that melatonin can suppress BVDV proliferation in MDBK cells by modulating the endoplasmic reticulum (ER) stress-mediated NF-κB pathway and autophagy. Specifically, melatonin alleviated ER stress, inhibited the activation of IκBα and p65, regulated autophagy, and reduced the expression levels of pro-inflammatory cytokines. Further, when we treated BVDVinfected cells with the ER stress inducer thapsigargin, it led to significant activation of the NF-κB pathway and autophagy. Conversely, treating the cells with the ER stress inhibitor 4-phenylbutyric acid reversed these effects. These findings suggest that melatonin exerts its antiviral effects primarily through the PERK-eIF2α-ATF4 of ER stress-mediated NF-κB pathway and autophagy. Overall, our study underscores the potential of melatonin as an effective protective and therapeutic option against BVDV, offering insights into its anti-infective mechanisms.

    Keywords: BVDV1, Melatonin2, PERK-eIF2α-ATF43, NF-κB pathway4, autophagy5

    Received: 13 May 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Zhao, Wang, Zhang, Wu, Wang 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:
    Xue-Fei Wang, China Agricultural University, Beijing, China
    Jia-Lu Zhang, China Agricultural University, Beijing, China
    Yi Wu, China Agricultural University, Beijing, China
    Jing Wang, Zhejiang Agriculture and Forestry University, Hangzhou, 311300, Zhejiang Province, China
    Jiufeng Wang, China Agricultural University, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.