ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
This article is part of the Research TopicIntegrated Genomic and Systems Approaches to Unravel Host-Virus Interactions in Viral Infectious DiseasesView all 3 articles
Modulation of viral replication, autophagy and apoptosis by induction and mutual regulation of transcription factors EB and E3 during coronavirus infection
Provisionally accepted
- 1Integrative Microbiology Research Centre, College of Agriculture, South China Agricultural University, Guangzhou, Guangdong, China
- 2Zhaoqing Branch Center of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology, Zhaoqing, Guangdong Province, China
- 3College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, China
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Viral invasion and replication in cells significantly impact lysosome structure and function. By sensing changes in the lysosome status, cascades of cellular responses are triggered to maintain lysosomal homeostasis. Two key regulators, transcription factors EB (TFEB) and E3 (TFE3), play essential regulatory roles in these processes by shuttling between the cytoplasm and the nucleus. In this study, we report that infection of cells and/or chickens by gammacoronavirus infectious bronchitis virus (IBV), human betacoronavirus OC43 (HCoV-OC43), and alphacoronavirus porcine epidemic diarrhea virus (PEDV) upregulates the expression of TFEB/TFE3 as well as their downstream targets, and induces the lysosomal stress response. Knockdown of TFE3 alone or together with TFEB demonstrated a pronounced role played by TFE3 in regulating viral replication, virus-induced autophagy and apoptosis in cells infected with the three viruses, and a synergistic effect of TFEB and TFE3 in cells infected with IBV and HCoV-OC43. Furthermore, inhibition of the biosynthetic secretory pathway with brefeldin A (BFA) demonstrated that the release of HCoV-OC43 is mainly via the lysosomal pathway. This study provides novel insights into the functional roles of the lysosomal biogenesis and stress response in coronavirus replication and virus-host interactions.
Keywords: Coronaviruses, Lysosomal stress response, TFEB, TFE3, Apoptosis
Received: 10 Apr 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Yang, Fung, Yuan, Chen and Liu. 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: Ding Xiang Liu
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