HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19

Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for...

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Veröffentlicht in:Signal transduction and targeted therapy 2021-08, Vol.6 (1), p.308-308, Article 308
Hauptverfasser: Tian, Mingfu, Liu, Weiyong, Li, Xiang, Zhao, Peiyi, Shereen, Muhammad Adnan, Zhu, Chengliang, Huang, Shanyu, Liu, Siyu, Yu, Xiao, Yue, Miaomiao, Pan, Pan, Wang, Wenbiao, Li, Yongkui, Chen, Xulin, Wu, Kailang, Luo, Zhen, Zhang, Qiwei, Wu, Jianguo
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Sprache:eng
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Zusammenfassung:Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.
ISSN:2059-3635
2095-9907
2059-3635
DOI:10.1038/s41392-021-00726-w