SARS-CoV-2 inhibits EBV-dependent tumor proliferation through PLpro-mediated degradation of EBNA1
5 affiliations
- 1The Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
- 2The Center for Infection and Immunity Study, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
- 3School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
- 4State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
- 5The Division of Basic Research, Guangzhou National Laboratory, Bio-island, Guangzhou 510320, China
Abstract
Co-circulation of multiple viruses within a host can produce pathological outcomes distinct from those of single-virus infections. Over 700 million documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during the coronavirus disease 2019 (COVID-19) pandemic indicate frequent co-circulation of SARS-CoV-2 with other human viruses. However, how SARS-CoV-2 infection influences other viral infections remains unclear. In this study, we investigated how the proteolytic activity of SARS-CoV-2 papain-like protease (PLpro) influences infection by other human viruses. In silico analysis identified candidate PLpro cleavage sites across numerous viral proteins, and biochemical assays confirmed that PLpro catalyzes the degradation of Epstein–Barr virus (EBV) nuclear antigen 1 (EBNA1) in a manner requiring its protease activity. Both ectopic PLpro expression and SARS-CoV-2 infection reduced EBNA1 abundance, leading to reactivation of latent EBV. Given the essential role of EBNA1 in maintaining EBV-associated tumorigenesis, SARS-CoV-2 and PLpro-mediated degradation of EBNA1 can be translated into an inhibitory effect on EBV-driven tumor proliferation. These findings establish a molecular mechanism by which SARS-CoV-2 PLpro disrupts EBV latency and suppresses EBV-associated tumorigenesis, positioning EBNA1 as a potential therapeutic target in EBV-related malignancies.
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BibTeX
@article{du2026sarscov2,
title = {{SARS-CoV-2 inhibits EBV-dependent tumor proliferation through PLpro-mediated degradation of EBNA1}},
author = {Liubing Du and Mengxuan Wang and Xue Liu and Ziliang Peng and Zhihui Zhang and Zhanjia Zhang and Zhijuan Liang and Qingrong Sun and Jiaxin Zhuang and Kongyang Ma and Yao-Qing Chen and Panpan Hou and Hua Zhang and Deyin Guo and Ji-An Pan and Xiaoxue Peng},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jul,
doi = {10.1016/j.apsb.2026.07.042},
url = {https://europepmc.org/article/PMC/PMC13729527},
note = {CC BY},
}
RIS
TY - JOUR
TI - SARS-CoV-2 inhibits EBV-dependent tumor proliferation through PLpro-mediated degradation of EBNA1
AU - Liubing Du
AU - Mengxuan Wang
AU - Xue Liu
AU - Ziliang Peng
AU - Zhihui Zhang
AU - Zhanjia Zhang
AU - Zhijuan Liang
AU - Qingrong Sun
AU - Jiaxin Zhuang
AU - Kongyang Ma
AU - Yao-Qing Chen
AU - Panpan Hou
AU - Hua Zhang
AU - Deyin Guo
AU - Ji-An Pan
AU - Xiaoxue Peng
PY - 2026
DA - 2026/07/30
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.07.042
UR - https://europepmc.org/article/PMC/PMC13729527
AB - Co-circulation of multiple viruses within a host can produce pathological outcomes distinct from those of single-virus infections. Over 700 million documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during the coronavirus disease 2019 (COVID-19) pandemic indicate frequent co-circulation of SARS-CoV-2 with other human viruses. However, how SARS-CoV-2 infection influences other viral infections remains unclear. In this study, we investigated how the proteolytic activity of SARS-CoV-2 papain-like protease (PLpro) influences infection by other human viruses. In silico analysis identified candidate PLpro cleavage sites across numerous viral proteins, and biochemical assays confirmed that PLpro catalyzes the degradation of Epstein–Barr virus (EBV) nuclear antigen 1 (EBNA1) in a manner requiring its protease activity. Both ectopic PLpro expression and SARS-CoV-2 infection reduced EBNA1 abundance, leading to reactivation of latent EBV. Given the essential role of EBNA1 in maintaining EBV-associated tumorigenesis, SARS-CoV-2 and PLpro-mediated degradation of EBNA1 can be translated into an inhibitory effect on EBV-driven tumor proliferation. These findings establish a molecular mechanism by which SARS-CoV-2 PLpro disrupts EBV latency and suppresses EBV-associated tumorigenesis, positioning EBNA1 as a potential therapeutic target in EBV-related malignancies.
SN - 2211-3835
SN - 2211-3843
ER -