TRIM23 prevents adenovirus replication by p62-mediated selective autophagic degradation of viral E1A protein
4 affiliations
- 1Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China
- 2Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- 3Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu, China
- 4Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, China
Abstract
The E3 ubiquitin ligase TRIM23 is involved in diverse cellular processes, however, its function in antiviral defense against adenovirus remains unclear. Here, we identify a novel mechanism by which TRIM23 restricts human adenovirus type 5 (HAdV-C5) replication. TRIM23 expression was upregulated upon HAdV-C5 infection, and functional studies showed that its overexpression inhibited viral replication, while knockdown enhanced it. Mechanistically, TRIM23 interacts with the viral E1A protein and promotes its degradation through a mechanism dependent of its canonical E3 ligase activity. Moreover, TRIM23 recruits the selective autophagy receptor p62 promotes E1A degradation in a E1A ubiquitination-independent manner. Our results unveil a novel host defense pathway-the TRIM23-E1A-p62 axis-that highlights the role of selective autophagy in antiviral immunity. Author summary: Elucidating virus-host interactions is critical for developing therapies against HAdV-C5. This study reveals that TRIM23 plays an antiviral role independent of its ubiquitination function. Depending on its E3 ligase activity, TRIM23 counteracts HAdV-C5 by directing viral E1A to autophagic degradation via p62, thereby circumventing typical ubiquitin-proteasome mediated signaling. These findings expand our understanding of how selective autophagy restricts viral infection and uncover a previously unrecognized layer of host defense centered on the TRIM23-E1A-p62 axis.
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BibTeX
@article{sun2026trim23,
title = {{TRIM23 prevents adenovirus replication by p62-mediated selective autophagic degradation of viral E1A protein}},
author = {Nan Sun and Jikai Zhang and Banruo Xia and Hang Yin and Jiaqian Xie and Xiaoxiao Liu and Man Li and Lin Fang and Guijuan Ji and Gaolei Ma and Haihan Zhang and Zhenzhen Wang and Dafei Chai and Gang Wang},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014578},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014578},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TRIM23 prevents adenovirus replication by p62-mediated selective autophagic degradation of viral E1A protein
AU - Nan Sun
AU - Jikai Zhang
AU - Banruo Xia
AU - Hang Yin
AU - Jiaqian Xie
AU - Xiaoxiao Liu
AU - Man Li
AU - Lin Fang
AU - Guijuan Ji
AU - Gaolei Ma
AU - Haihan Zhang
AU - Zhenzhen Wang
AU - Dafei Chai
AU - Gang Wang
PY - 2026
DA - 2026/09/08
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014578
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014578
AB - The E3 ubiquitin ligase TRIM23 is involved in diverse cellular processes, however, its function in antiviral defense against adenovirus remains unclear. Here, we identify a novel mechanism by which TRIM23 restricts human adenovirus type 5 (HAdV-C5) replication. TRIM23 expression was upregulated upon HAdV-C5 infection, and functional studies showed that its overexpression inhibited viral replication, while knockdown enhanced it. Mechanistically, TRIM23 interacts with the viral E1A protein and promotes its degradation through a mechanism dependent of its canonical E3 ligase activity. Moreover, TRIM23 recruits the selective autophagy receptor p62 promotes E1A degradation in a E1A ubiquitination-independent manner. Our results unveil a novel host defense pathway-the TRIM23-E1A-p62 axis-that highlights the role of selective autophagy in antiviral immunity. Author summary: Elucidating virus-host interactions is critical for developing therapies against HAdV-C5. This study reveals that TRIM23 plays an antiviral role independent of its ubiquitination function. Depending on its E3 ligase activity, TRIM23 counteracts HAdV-C5 by directing viral E1A to autophagic degradation via p62, thereby circumventing typical ubiquitin-proteasome mediated signaling. These findings expand our understanding of how selective autophagy restricts viral infection and uncover a previously unrecognized layer of host defense centered on the TRIM23-E1A-p62 axis.
SN - 1553-7374
ER -