Competitive Endogenous RNA Network Activates Host Immune Response in SARS-CoV-2-, panH1N1 (A/California/07/2009)-, and H7N9 (A/Shanghai/1/2013)-Infected Cells.

Minghui Yang,Jin Li,Yun Peng,Jun Wang,Fuxiang Wang,Shoulong Deng,Hao Fan,Xiao Jiang,Ling Qing,Zhixiang Xu,Yingxia Liu,Yang Yang,Jinli Wei,Guoguo Ye

doi:10.3390/cells11030487

Abstract

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to infect human beings in late December 2019, in Wuhan, China, and Coronavirus disease 2019(COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World HealthOrganization (WHO) on 11 March 2020 [1,2]
We established nine cDNA libraries from SARS-CoV-2, pandemic H1N1 (panH1N1), and H7N9-infected cells collected at 60 h.p.i. with three replicates for each group and identified 149,777 mRNAs in total
It is worth mentioning that we found that Interferon regulatory factor-1 (IRF1) was significantly upregulated in SARS-CoV-2-infected lung cells [30,31,32,33,34], which indicated that IRF1 might play an important role in inflammatory and interferon response after SARS-CoV-2 infection (Figure S2)

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to infect human beings in late December 2019, in Wuhan, China, and Coronavirus disease 2019(COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World HealthOrganization (WHO) on 11 March 2020 [1,2]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to infect human beings in late December 2019, in Wuhan, China, and Coronavirus disease 2019. (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health. Asymptomatic infections account for 13–30.8% of all SARS-CoV-2 infections, and silent transmission during the presymptomatic and asymptomatic stages is responsible for more than 50% of the overall attack rate in COVID-19 outbreaks [3,4,5]. 16–21% of COVID-19 patients have become severely ill, of which there has been a 2–3% mortality rate [7,8,9,10]. There were recent outbreaks of new influenza strains, such as the 2009 pandemic H1N1 (panH1N1), which emerged in North

Methods

Results

Conclusion