Atypical activation of the RNA sensor MDA5 by hepatitis C virus.
Surajit ChakrabortyJunji ZhuMichaela U GackPublished in: The FEBS journal (2023)
Hepatitis C virus (HCV) is a significant human pathogen that can cause a number of serious diseases including chronic inflammation of the liver, cirrhosis, and hepatocellular carcinoma. A key enzyme in the HCV life cycle is the nonstructural protein 5B (NS5B), which functions as an RNA-dependent RNA polymerase (RdRp) responsible for replicating the viral RNA genome. In their recent study, Dansako and colleagues showed that HCV NS5B induces type I interferon via activation of the RNA receptor MDA5, an activity that was dependent on the RdRp enzymatic activity but independent of viral RNA replication. Their data further indicated that the NS5B enzymes of HCV and the related GB virus-B produce cellular double-stranded RNA (dsRNA) species with potential immunostimulatory activity. These findings unveil an unconventional mechanism of activation of MDA5-mediated host immunity by viral RdRp enzymes, which is expected to spur new research directions in viral immunology.
Keyphrases
- binding protein
- hepatitis c virus
- human immunodeficiency virus
- sars cov
- nucleic acid
- breast cancer cells
- dengue virus
- endothelial cells
- life cycle
- oxidative stress
- gene expression
- signaling pathway
- electronic health record
- cell proliferation
- artificial intelligence
- climate change
- immune response
- zika virus
- risk assessment
- candida albicans
- amino acid
- pi k akt