NSUN2-mediated m5C modification of HIV-1 RNA enables evasion of RIG‑I‑dependent innate immunity.

m5C modification of HIV-1 RNA by NSUN2 enables the virus to evade RIG-I detection and enhances replication, with a 50% reduction in immune evasion when NSUN2 is depleted.

• Why it matters: Understanding how HIV-1 evades innate immunity is crucial for developing new antiviral strategies, as current knowledge of RNA modifications in immune escape is limited.
• What they did: The study used NSUN2 depletion and in vitro transcription to analyze m5C modification effects, demonstrating that modified RNA reduces IFN-I induction and RIG-I binding.
• The result: HIV-1’s m5C modification suppresses immune detection, promoting viral replication; targeting this modification pathway could improve antiviral responses.