tetano
Editor, Senior Moderator
Front Immunol
. 2025 Aug 15:16:1619538.
doi: 10.3389/fimmu.2025.1619538. eCollection 2025. A fusion ORF3a-E subgenomic RNA involved in SARS-CoV-2 infection efficacy by influencing cellular protein synthesis
Yifan Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Jing Li[SUP] #[/SUP][SUP] 1 [/SUP], Xinglong Zhang[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Jiali Li[SUP] 1 [/SUP], Heng Li[SUP] 1 2 3 [/SUP], Xin Zhao[SUP] 1 2 3 [/SUP], Zihan Zhang[SUP] 1 [/SUP], Yingyan Li[SUP] 1 [/SUP], Keqi Chen[SUP] 1 [/SUP], Shasha Peng[SUP] 1 [/SUP], Haijing Shi[SUP] 1 2 3 [/SUP], Longding Liu[SUP] 1 2 3 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; ribosome; single-cell sequence; subgenomic RNA; viral replication.
. 2025 Aug 15:16:1619538.
doi: 10.3389/fimmu.2025.1619538. eCollection 2025. A fusion ORF3a-E subgenomic RNA involved in SARS-CoV-2 infection efficacy by influencing cellular protein synthesis
Yifan Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Jing Li[SUP] #[/SUP][SUP] 1 [/SUP], Xinglong Zhang[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Jiali Li[SUP] 1 [/SUP], Heng Li[SUP] 1 2 3 [/SUP], Xin Zhao[SUP] 1 2 3 [/SUP], Zihan Zhang[SUP] 1 [/SUP], Yingyan Li[SUP] 1 [/SUP], Keqi Chen[SUP] 1 [/SUP], Shasha Peng[SUP] 1 [/SUP], Haijing Shi[SUP] 1 2 3 [/SUP], Longding Liu[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 40895568
- PMCID: PMC12395053
- DOI: 10.3389/fimmu.2025.1619538
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.
Keywords: SARS-CoV-2; ribosome; single-cell sequence; subgenomic RNA; viral replication.