A fusion ORF3a-E subgenomic RNA involved in SARS-CoV-2 infection efficacy by influencing cellular protein synthesis

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,...

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Main Authors: Yifan Zhang, Jing Li, Xinglong Zhang, Xin Zhang, Jiali Li, Heng Li, Xin Zhao, Zihan Zhang, Yingyan Li, Keqi Chen, Shasha Peng, Haijing Shi, Longding Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1619538/full
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Summary: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-2-infected 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.
ISSN:1664-3224