ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1619538
This article is part of the Research TopicImmunological Regulation to Enteroviruses and Respiratory Viruses: Infection and Vaccination ResponsesView all 9 articles
A fusion ORF3a-E subgenomic RNA involveed in SARS-CoV-2 infectionefficacy by influencing cellular protein synthesis
Provisionally accepted
YiFan Zhang
Jing LiXinglong Zhangxin zhangJiali Li
Heng LiXin ZhaoZihan ZhangYingyan LiKeqi ChenShasha PengHaijing Shi
Longding Liu*- Peking Union Medical College Graduate School, Beijing, China
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Subgenomic RNAs (sgRNAs) are discontinuous transcription products of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are involved in viral gene expression and replication, but their exact functions are still being studied. Here, we report the identification of a nested ORF3a-sgRNA, the fusion ORF3a-E-sgRNA, which is involved in the infection process of SARS-CoV-2. This sgRNA encodes both ORF3a and E and can be detected throughout the viral life cycle in SARS-CoV-2infected cells with high copy numbers. ORF3a-E-sgmRNA guides ORF3a translation and promotes the expression of cellular ribosomal protein S3 (RPS3), increasing translation levels. Single-cell sequencing of a SARS-CoV-2-infected human bronchial epithelial cell line (16HBE) revealed that maintenance of this stable translational environment by ORF3a-E-sgmRNA is important for SARS-CoV-2 assembly and release capabilities and is also beneficial for viral evasion of host innate immunity.More importantly, the transcription level of ORF3a-E-sgRNA may contribute to differences in infection processes between the Wuhan strain and the XBB strain of SARS-CoV-2.
Keywords: SARS-CoV-2, Subgenomic RNA, ribosome, viral replication, single-cell sequence
Received: 28 Apr 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Zhang, Li, Zhang, zhang, Li, Li, Zhao, Zhang, Li, Chen, Peng, Shi 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: Longding Liu, Peking Union Medical College Graduate School, Beijing, China
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