1. Verification of SARS-CoV-2-Encoded small RNAs and contribution to Infection-Associated lung inflammation
- Author
-
Nan Xiang Geng, Wei Zhu, Biao Lun Cui, Li Bao Zhu, Xing Chang Luan, Jiang Lin, Rui Xu, Yan Chen, Cheng Liu, Cheng Zhang, Yu Chun Li, and Xin Guo Song
- Subjects
Lung ,biology ,viruses ,fungi ,RNA virus ,respiratory system ,biology.organism_classification ,medicine.disease ,Virology ,Virus ,respiratory tract diseases ,medicine.anatomical_structure ,Type I interferon signaling pathway ,medicine ,Coronaviridae ,CXCL11 ,Interleukin 8 ,Cytokine storm - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. SARS-CoV-2 is a positive-stranded RNA virus belongs to Coronaviridae family. The viral genome of SARS-CoV-2 contains around 29.8 kilobase with a 5′-cap structure and 3′-poly-A tail, and shows 79.2% nucleotide identity with human SARS-CoV-1, which caused the 2002-2004 SARS outbreak. As the successor to SARS-CoV-1, SARS-CoV-2 now has circulated across the globe. There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. In this study, we verified the existence of two 18-22 nt small viral RNAs (svRNAs) derived from the same precursor in human specimens infected with SARS-CoV-2, including nasopharyngeal swabs and formalin-fixed paraffin-embedded (FFPE) explanted lungs from lung transplantation of COVID-19 patients. We then simulated and confirmed the formation of these two SARS-CoV-2-Encoded small RNAs in human lung epithelial cells. And the potential pro-inflammatory effects of the splicing and maturation process of these two svRNAs in human lung epithelial cells were also explored. By screening cytokine storm genes and the characteristic expression profiling of COVID-19 in the explanted lung tissues and the svRNAs precursor transfected human lung epithelial cells, we found that the maturation of these two small viral RNAs contributed significantly to the infection associated lung inflammation, mainly via the activation of the CXCL8, CXCL11 and type I interferon signaling pathway. Taken together, we discovered two SARS-CoV-2-Encoded small RNAs and investigated the pro-inflammatory effects during their maturation in human lung epithelial cells, which might provide new insight into the pathogenesis and possible treatment options for COVID-19.
- Published
- 2021