| First Author | Kong X | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 1 | Pages | 112002 |
| PubMed ID | 36662617 | Mgi Jnum | J:342798 |
| Mgi Id | MGI:7434064 | Doi | 10.1016/j.celrep.2023.112002 |
| Citation | Kong X, et al. (2023) Type I interferon/STAT1 signaling regulates UBE2M-mediated antiviral innate immunity in a negative feedback manner. Cell Rep 42(1):112002 |
| abstractText | Type I interferon (IFN-I) signaling is central to inducing antiviral innate immunity. However, the mechanisms for IFN-I signaling self-regulation are still largely unknown. Here, we report that RNA virus-infected macrophages with UBE2M deficiency produced decreased IFN-I expression in a RIG-I-dependent manner, causing an aggravated viral infection. Mechanistically, UBE2M inhibits RIG-I degradation by preventing the interaction of RIG-I and E3 ligase STUB1, resulting in antiviral IFN-I signaling activation. Simultaneously, IFN-I signaling-activated STAT1 facilitates the transcription of Trim21, leading to increased UBE2M degradation and blunted antiviral immunity. Translationally, oral administration of milk-derived extracellular vesicles containing RING domain-truncated TRIM21 (TRIM21-DeltaRING) lacking E3 ligase activity efficiently transfers TRIM21-DeltaRING into macrophages. TRIM21-DeltaRING suppresses UBE2M degradation by competitively binding to UBE2M with TRIM21, thereby enhancing antiviral immunity. Overall, we reveal a negative feedback loop of IFN-I signaling and develop a reagent to improve innate immunity against RNA viruses. |
