Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2 - PubMed
5 hours ago
- #RNA Polymerase III
- #Mitochondrial DNA
- #COVID-19
- Defective RNA Polymerase III (POL III) sensing of mitochondrial DNA (mtDNA) in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.
- Identified 10 rare, monoallelic predicted loss-of-function variants in POLR3A and POLR3C genes in 18 patients with critical COVID-19.
- POL III haploinsufficiency leads to impaired type I IFN responses to mtDNA or SARS-CoV-2 infection, increasing viral replication.
- SARS-CoV-2 induces mtDNA release via oligomerization of the mitochondrial voltage-dependent anion channel under oxidative stress, enabling POL III-mtDNA interaction.
- Autosomal dominant POL III haploinsufficiency may predispose individuals to critical COVID-19.