The Novel Viral Non‐Coding RNA LMP2A‐IT1 Promotes the Lytic Replication of EBV
5 affiliations
- 1State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat‐sen University Cancer Center Guangzhou China
- 2State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases Gannan Innovation and Translational Medicine Research Institute Gannan Medical University Ganzhou China
- 3Department of Clinical Laboratory State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou China
- 4Department of Pathology Sun Yat‐sen University Cancer Center Guangzhou China
- 5Guangdong‐Hong Kong Joint Laboratory for RNA Medicine Sun Yat‐sen University Guangzhou China
Abstract
The Epstein‐Barr virus (EBV) is recognized as the first human tumor virus and etiologically linked to a spectrum of malignancies and autoimmune diseases. EBV lytic replication contributes substantially to pathogenesis, but the viral components that enable efficient replication within host cells remain incompletely understood. Here, we identified a previously unknown EBV non‐coding RNA (ncRNA) from glycoRNA samples and designated it LMP2A‐IT1. This viral ncRNA was consistently detected across multiple EBV‐infected cell lines, in exosomes, and in EBV‐positive nasopharyngeal carcinoma tissues, exhibiting a predominantly cytoplasmic distribution. Functional analyses reveal that the induction of LMP2A‐IT1 during EBV lytic replication actively drives the lytic cycle, resulting in a self‐amplifying positive feedback loop. Mechanistically, LMP2A‐IT1 appears to activate an inflammatory response, which subsequently upregulates BZLF1, a master regulator of the EBV lytic cascade, to facilitate lytic progression. Together, our findings suggest that LMP2A‐IT1 represents a previously unrecognized viral factor that EBV deploys to achieve robust replication. To our best knowledge, this is the first report of a viral RNA harboring glycosylation modifications, thereby expanding the glycoRNA landscape. Moreover, this study offers new mechanistic insights into EBV replication as well as a potential biomarker and therapeutic target for EBV‐associated diseases.
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BibTeX
@article{lu2026novel,
title = {{The Novel Viral Non‐Coding RNA LMP2A‐IT1 Promotes the Lytic Replication of EBV}},
author = {Zheng‐Zhou Lu and Jun‐Fei Wu and Nannan Zhu and Ming‐Hui Yang and Le‐Le Zhang and Yuan‐Tao Liu and Wei‐Jun Chen and Jin‐Kun Tang and Jia‐Wei Ge and Chao‐Bo Lei and Tao Zhang and Yu Wang and Chao‐Yun Huang and Qian Zhong and Mu‐Sheng Zeng and Yan Li},
journal = {Advanced Science},
year = {2026},
month = nov,
doi = {10.1002/advs.78488},
url = {https://doi.org/10.1002/advs.78488},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Novel Viral Non‐Coding RNA LMP2A‐IT1 Promotes the Lytic Replication of EBV
AU - Zheng‐Zhou Lu
AU - Jun‐Fei Wu
AU - Nannan Zhu
AU - Ming‐Hui Yang
AU - Le‐Le Zhang
AU - Yuan‐Tao Liu
AU - Wei‐Jun Chen
AU - Jin‐Kun Tang
AU - Jia‐Wei Ge
AU - Chao‐Bo Lei
AU - Tao Zhang
AU - Yu Wang
AU - Chao‐Yun Huang
AU - Qian Zhong
AU - Mu‐Sheng Zeng
AU - Yan Li
PY - 2026
DA - 2026/11/05
JO - Advanced Science
DO - 10.1002/advs.78488
UR - https://doi.org/10.1002/advs.78488
AB - The Epstein‐Barr virus (EBV) is recognized as the first human tumor virus and etiologically linked to a spectrum of malignancies and autoimmune diseases. EBV lytic replication contributes substantially to pathogenesis, but the viral components that enable efficient replication within host cells remain incompletely understood. Here, we identified a previously unknown EBV non‐coding RNA (ncRNA) from glycoRNA samples and designated it LMP2A‐IT1. This viral ncRNA was consistently detected across multiple EBV‐infected cell lines, in exosomes, and in EBV‐positive nasopharyngeal carcinoma tissues, exhibiting a predominantly cytoplasmic distribution. Functional analyses reveal that the induction of LMP2A‐IT1 during EBV lytic replication actively drives the lytic cycle, resulting in a self‐amplifying positive feedback loop. Mechanistically, LMP2A‐IT1 appears to activate an inflammatory response, which subsequently upregulates BZLF1, a master regulator of the EBV lytic cascade, to facilitate lytic progression. Together, our findings suggest that LMP2A‐IT1 represents a previously unrecognized viral factor that EBV deploys to achieve robust replication. To our best knowledge, this is the first report of a viral RNA harboring glycosylation modifications, thereby expanding the glycoRNA landscape. Moreover, this study offers new mechanistic insights into EBV replication as well as a potential biomarker and therapeutic target for EBV‐associated diseases.
SN - 2198-3844
ER -