Int J Med Sci 2021; 18(12):2561-2569. doi:10.7150/ijms.56630 This issue

Research Paper

SARS-CoV-2 infection activates a subset of intrinsic pathways to inhibit type I interferons in vitro and in vivo

Weisheng Luo1,2, Lianzhou Huang1,2, Xiaohui Wang1,2, Yuying Ma1,2, Ji Xiao1,2, Xiaowei Song1,2, Ping Liu1,2, Yifei Wang1,2✉, Yiliang Wang1,2✉, Zhe Ren1,2✉

1. Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
2. Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou 510632, PR China.

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Citation:
Luo W, Huang L, Wang X, Ma Y, Xiao J, Song X, Liu P, Wang Y, Wang Y, Ren Z. SARS-CoV-2 infection activates a subset of intrinsic pathways to inhibit type I interferons in vitro and in vivo. Int J Med Sci 2021; 18(12):2561-2569. doi:10.7150/ijms.56630. Available from https://www.medsci.org/v18p2561.htm

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Abstract

Graphic abstract

SARS-CoV-2 infection poses a global challenge to human health. Upon viral infection, host cells initiate the innate antiviral response, which primarily involves type I interferons (I-IFNs), to enable rapid elimination of the invading virus. Previous studies revealed that SARS-CoV-2 infection limits the expression of I-IFNs in vitro and in vivo, but the underlying mechanism remains incompletely elucidated. In the present study, we performed data mining and longitudinal data analysis using SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells and ferrets, and the results confirmed the strong inhibitory effect of SARS-CoV-2 on the induction of I-IFNs. Moreover, we identified genes that are negatively correlated with IFNB1 expression in vitro and in vivo based on Pearson correlation analysis. We found that SARS-CoV-2 activates numerous intrinsic pathways, such as the circadian rhythm, phosphatidylinositol signaling system, peroxisome, and TNF signaling pathways, to inhibit I-IFNs. These intrinsic inhibitory pathways jointly facilitate the successful immune evasion of SARS-CoV-2. Our study elucidates the underlying mechanism by which SARS-CoV-2 evades the host innate antiviral response in vitro and in vivo, providing theoretical evidence for targeting these immune evasion-associated pathways to combat SARS-CoV-2 infection.

Keywords: SARS-CoV-2, innate antiviral responses, type I IFNs, immune evasion