HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19.
Signal Transduct Target Ther
; 6(1): 308, 2021 08 18.
Article
in En
| MEDLINE
| ID: mdl-34408131
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Viroporin Proteins
/
SARS-CoV-2
/
COVID-19
/
Mitochondria
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Signal Transduct Target Ther
Year:
2021
Document type:
Article
Affiliation country:
China