NSUN2-mediated HCV RNA m5C Methylation Facilitates Viral RNA Stability and Replication.

ABSTRACT: RNA modifications have emerged as new efficient targets against viruses. However, little is known about 5-methylcytosine (m5C) modification in the genomes of flaviviruses. Herein, we demonstrate that hepatitis C virus (HCV), dengue virus, and Zika virus exhibit high levels of viral RNA m5C modification. We identified an m5C site at C7525 in the NS5A gene of the HCV RNA genome. HCV infection upregulates the expression of the host m5C methyltransferase NSUN2 via the transcription factor E2F1. NSUN2 deficiency decreases HCV RNA m5C methylation levels, which further reduces viral RNA stability, replication, and viral assembly and budding. A C7525-specific m5C-abrogating mutation in the HCV RNA genome similarly reduces viral replication, assembly, and budding by decreasing viral RNA stability.

SUBMITTER: Li ZL 

PROVIDER: S-EPMC12233092 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature