A fish-specific E3 ubiquitin ligase NHRE3 suppresses antiviral immunity by degrading ISG15 via ubiquitination.

Fish-specific E3 ubiquitin ligase NHRE3 degrades ISG15, suppressing antiviral immunity and facilitating GCRV infection in grass carp and rare minnow.

• Why it matters: Understanding how viruses evade host immune responses is crucial for developing effective treatments and managing fish diseases, especially given the limited knowledge of fish antiviral mechanisms.
• What they did: Researchers identified NHRE3 as a fish-specific E3 ubiquitin ligase that interacts with and catalyzes K48-linked polyubiquitination of ISG15, leading to its degradation; nhre3-/- rare minnows showed increased resistance to GCRV.
• The result: The study reveals a unique fish-specific immune evasion pathway where NHRE3 promotes viral infection by degrading ISG15, highlighting an ancient and diverse mechanism of innate immune regulation in vertebrates.