TRIM proteins: A ‘swiss army knife’ of antiviral immunity
Fig 5
Examples of viruses escaping the restriction mediated by TRIM proteins.
Left side: Viruses inhibit the antiviral action of TRIMs. NS1 protein of Influenza A virus (IAV) impairs the activation of RIG-I by TRIM25 [56]. TRIM23 is antagonized by HSV proteins γ134.5 [45] and Us11 [63], removing the restriction on HSV expression and blocking autophagy initiation. IE1 protein of human cytomegalovirus (HMCV) impedes the SUMOylation of TRIM19, leading to nuclear body (NB) disruption and release of viral proteins [58]. Right side: Viruses take advantages of TRIM-mediated modifications. Polyubiquitination of the Zika virus (ZIKV) envelope protein promotes its interaction with the TIM-1 receptor [64]. TRIM6-mediated modification of VP35 stabilizes L polymerase on the Ebola virus (EBOV) genome [65]. In addition, TRIM6 facilitates the association of the nucleoprotein (NP) of SARS-CoV-2 with the viral genome [67]. TRIM44 promotes the initiation of autophagy, which facilitates RABV replication [68]. Human papillomavirus (HPV) E7 protein enables polyubiquitination of IFI16 by TRIM21, inhibiting inflammasome assembly and pyroptosis [70]. Created in BioRender. Lucifora, J. (2025) https://BioRender.com/q85j502.