Table 1.
The Role of TRIM Proteins in Innate Immunity
| TRIM Protein | Function in Innate Immunity | Viruses Affected | Mechanism | References |
|---|---|---|---|---|
| TRIM1 | Restriction of retroviruses through initiation of innate immune signaling | N-MLV | Yap et al. (2004) | |
| TRIM4 | Ubiquitination of RIG-I in cooperation with TRIM25 | SeV, VSV | Yan et al. (2014); Sun et al. (2016) | |
| TRIM5 | Restriction of retroviruses and innate immune signaling upon capsid recognition | HIV-1, N-MLV, EIAV | Capsid binding via the PRYSPRY domain, autoubiquitination and proteasomal recruitment, stimulation of signaling pathways through unanchored K63 ubiquitin chains | Lukic et al. (2011); Pertel et al. (2011); Stremlau et al. (2004); Grütter and Luban (2012) |
| TRIM6 | Regulation of the IRF3 signaling pathway | SeV, IAV, ECMV | Generation of unanchored K48-linked ubiquitin chains that activate IKKɛ for STAT1 phosphorylation | Rajsbaum et al. (2014); Bharaj et al. (2016) |
| TRIM8 | Positive regulation of NF-κB target genes IL-1β and TNFα | K63-linked ubiquitination and subsequent activation of TAK-1 | Okumura et al. (2010) | |
| Epinephelus coioides TRIM8 restricts Singapore grouper iridovirus (SGIV) | SGIV | Huang et al. (2016a) | ||
| TRIM9 short isoform | Positive regulation of IRF3 signaling pathway | VSV, HSV-1 | Autoubiquitination of TRIM9 facilitates GSK3β-mediated activation of TBK1 | Qin et al. (2016) |
| TRIM11 | Restriction of retroviruses | HIV-1 | Acceleration of HIV-1 uncoating which results in reduced reverse transcription | Yuan et al. (2014); Yuan et al. (2016) |
| Negative regulation of IFNβ production | HSV-1, VSV | Interaction with TBK1 | Lee et al. (2013) | |
| Negative regulation of the AIM2 inflammasome | HSV-1, MCMV | Interaction with AIM2 via the PRYSPRY domain, autoubiquitination and recruitment of p62 which results in AIM2 degradation by autophagy | Liu et al. (2016a) | |
| TRIM13 | Negative regulation of MDA5 signaling pathway, positive regulation of RIG-I pathway | ECMV, SeV | Narayan et al. (2014) | |
| Positive regulation of the TLR2-stimulated NF-κB signaling pathway | K29-linked polyubiquitination of TRAF6 | Huang and Baek (2017) | ||
| Negative regulation of NF-κB activation | Regulation of NEMO ubiquitination | Tomar and Singh (2014) | ||
| Epinephelus coioides TRIM13 negatively regulates IRF3 and MDA5 signaling pathways | RGNNV | Huang et al. (2016b) | ||
| TRIM14 | Positive regulation of the RLR signaling pathway | SeV | K63-linked polyubiquitination of TRIM14 after viral infection likely through interaction with MAVS results in recruitment of NEMO to the MAVS signalosome | Zhou et al. (2014) |
| Positive regulation of cGAS-dependent type I IFN response | HSV-1, VSV | Recruitment of USP14 which deubiquitinates cGAS, thus preventing its p62-dependent autophagic degradation | Chen et al. (2016) | |
| Restriction of flaviviruses | HCV | Degradation of viral NS5A protein | Wang et al. (2016); Nenasheva et al. (2015) | |
| TRIM15 | Regulation of the RIG-I signaling pathway | VSV | Uchil et al. (2013) | |
| Restriction of retroviruses | HIV-1, N-MLV | Inhibition of viral release through interaction of the B-box with the Gag precursor protein | Uchil et al. (2008) | |
| TRIM19 (PML) | Restriction of retroviruses | HIV-1 | Interference with early steps of replication | Turelli et al. (2001) |
| Cell type-specific restriction early in the viral life cycle | Kahle et al. (2016) | |||
| Repression of viral transcription | Lusic et al. (2013); Masroori et al. (2016) | |||
| Stabilization of Daxx which then inhibits reverse transcription | Dutrieux et al. (2015) | |||
| Restriction of parvoviruses | AAV | Mitchell et al. (2014) | ||
| Restriction of herpesviruses | HCMV | Schilling et al. (2017); Wagenknecht et al. (2015) | ||
| Restriction of rhabdoviruses | VSV | Inhibition of viral protein synthesis | Chelbi-Alix et al. (1998) | |
| Positive regulation of IFNβ | VSV, SeV, ECMV, HTLV-1, IAV, VV | Recruitment of Pin1 into nuclear bodies which prevents degradation of IRF3 (Saitoh et al., 2006) | El Asmi et al. (2014) | |
| TRIM20 (pyrin) | Inflammasome activation | Inactivation of Rho GTPases results in loss of downstream pyrin phosphorylation. Phosphorylated pyrin is usually bound by inhibitory 14-3-3 proteins, and thus a loss of phosphorylation might result in activation | Richards et al. (2001); Yu et al. (2006); Masters et al. (2016); Manukyan and Aminov (2016); Park et al. (2016); Latsoudis et al. (2017); Xu et al. (2014); Vajjhala et al. (2014) | |
| Regulation of NF-κB signaling | Caspase-1 cleaves an N-terminal fragment of TRIM20 that results in ASC-dependent NF-κB activation | Chae et al. (2008) | ||
| TRIM21 | Restriction of adenoviruses | hAdV5, MAV-1 | Binding of the PRYSPRY domain to antibody-coated virus results in autoubiquitination and recruitment of the proteasome | Mallery et al. (2010); Vaysburd et al. (2013); Watkinson et al. (2013); Fletcher and James (2016) |
| Restriction of picornaviruses | FMDV | Fan et al. (2016a) | ||
| Innate immune sensing of viruses | hAdV5, HRV14, FCV | Release of K63-linked ubiquitin chains by proteasome-associated DUB Poh-1 | McEwan et al. (2013); Watkinson et al. (2015); Watkinson et al. (2013); Fletcher et al. (2014) | |
| Negative regulation of dsDNA cellular response | HSV-1 | K48-linked polyubiquitination and degradation of DDX41 | Zhang et al. (2012a) | |
| Negative regulation of IRF signaling pathways | SeV | Polyubiquitination and degradation of IRF3, IRF5, and IRF7 | Higgs et al. (2008); Lazzari et al. (2014); Higgs et al. (2010) | |
| Positive regulation of IRF signaling pathways | Preventing interaction between Pin1 and IRF3, thus preventing Pin1-dependent IRF3 degradation | Kong et al. (2007) | ||
| Ubiquitination of IRF8 results in increased ability to stimulate IL-12p40 expression | Kong et al. (2007) | |||
| TRIM22 | Restriction of retroviruses | HIV-1 | Singh et al. (2011); Barr et al. (2008) | |
| Transcriptional silencing | Turrini et al. (2015); Kajaste-Rudnitski et al. (2011) | |||
| Restriction of flaviviruses | HCV | Ubiquitination of NS5A | Yang et al. (2016) | |
| HBV | Transcriptional repression mediated by the RING and PRYSPRY domains | Yang et al. (2016) | ||
| Restriction of orthomyxoviruses | IAV | Degradation of the viral nucleoprotein | Di Pietro et al. (2013) | |
| TRIM23 | Regulation of NF-κB signaling | SeV | K27-linked polyubiquitination of NEMO | Arimoto et al. (2010) |
| Positive regulation of viral infectivity | YFV | Polyubiquitination of YFV NS5 promotes binding to STAT2 and suppresses type I IFN signaling | Laurent-Rolle et al. (2014) | |
| HCMV | Interaction with HCMV UL144 facilitates association with TRAF6, which activates NF-κB signaling | Poole et al. (2009) | ||
| TRIM25 | Positive regulation of the RIG-I pathway | NDV, VSV, SeV | Ubiquitination of the RIG-I CARDs, which facilitates the interaction with MAVS | Gack et al. (2007); Zeng et al. (2010); Sanchez et al. (2016) |
| Modulation of antiviral activity of zinc finger antiviral protein (ZAP) | SinV | Zheng et al. (2017); Li et al. (2017) | ||
| TRIM26 | Positive regulation of the RLR signaling pathway | NDV, VSV | Direct interaction with TBK and likely recruitment of NEMO through autoubiquitination bridges NEMO and TBK1 and positively regulates IFNβ | Ran et al. (2016) |
| Negative regulation of type I IFN signaling pathway | VSV | Polyubiquitination and degradation of IRF3 resulting in diminished IFNβ response | Wang et al. (2015a) | |
| TRIM27 | Negative regulation of NOD2-mediated NF-κB signaling | K48-linked ubiquitination and subsequent proteasomal degradation of NOD2 | Zurek et al. (2012) | |
| TRIM28 | Restriction of retroviruses | M-MLV | Transcriptional repression | Wolf and Goff (2007); Wolf and Goff (2007) |
| HIV-1 | Inhibition of HIV-1 integration | Allouch et al. (2011); Figueiredo and Hope (2011) | ||
| Negative regulation of the IRF7 signaling pathway | VSV | SUMOylation of IRF7 | Liang et al. (2011) | |
| TRIM29 | Negative regulation of NF-κB and type I IFN signaling pathways | IAV | Ubiquitination and subsequent degradation of NEMO in alveolar macrophages | Xing et al. (2016) |
| TRIM30 | Negative regulation of NF-κB signaling | TRIM30α facilitates degradation of TAB2 and TAB3 | Shi et al. (2008) | |
| Negative regulation of NLRP3 inflammasome activation | Attenuation of ROS production | Hu et al. (2010) | ||
| TRIM31 | Negative regulation of NLRP3 inflammasome activation | K48-linked ubiquitination and proteasomal degradation of NLRP3 | Song et al. (2016) | |
| Positive regulation of the RLR signaling pathway | SeV | K63-linked polyubiquitination of MAVS which promotes MAVS aggregation | Liu et al. (2017b) | |
| TRIM32 | Restriction of orthomyxoviruses | IAV | Ubiquitination and degradation of IAV PB1 polymerase | Fu et al. (2015) |
| Positive regulation of type I IFN signaling | VSV, NDV | K63-linked ubiquitination of STING which promotes interaction with TBK1 | Zhang et al. (2012b) | |
| TRIM33 | Activation of NLRP3 inflammasome in response to dsRNA | K63-linked ubiquitination of dsRNA sensor DHX33 (Gallouet et al., 2017) which results in DHX33–NLRP3 complex formation | Weng et al. (2014) | |
| Regulation of Ifnb1 expression in macrophages | Regulatory element at the Ifnb1 enhancer | Ferri et al. (2015) | ||
| TRIM35 | Negative regulation of type I IFN signaling in response to TLR9 and TLR7 activation | VSV, HSV-1 | K48-linked ubiquitination of IRF7 which results in proteasomal degradation | Wang et al. (2015b) |
| TRIM37 | Restriction of retroviruses | HIV-1 | Tabah et al. (2014) | |
| TRIM38 | Negative regulation of TLR3/4 signaling pathways | K48-linked polyubiquitination and subsequent proteasomal degradation of TRIF | Hu et al. (2015); Xue et al. (2012) | |
| K48-linked polyubiquitination and subsequent proteasomal degradation of TRAF6 | Zhao et al. (2012a) | |||
| VSV | K48-linked polyubiquitination and subsequent proteasomal degradation of NAP1 | Zhao et al. (2012b) | ||
| Negative regulation of IL-1β and TNFα induction | Proteasomal degradation of TAB2/3 | Hu et al. (2014) | ||
| Regulation of the cGAS signaling pathway | SUMOylation of cGAS and STING which results in increased stability | Hu et al. (2016) | ||
| TRIM40 | Negative regulation of NF-κB signaling | Inhibition of NEMO through its neddylation in the gastrointestinal tract | Noguchi et al. (2011) | |
| TRIM41 | Inhibition of flaviviruses | HBV | Inhibition of HBV transcription | Zhang et al. (2013) |
| TRIM44 | Positive regulation of RLR signaling pathway | SeV | Stabilization of MAVS | Yang et al. (2013) |
| TRIM45 | Negative regulation of NF-κB signaling | Shibata et al. (2012) | ||
| TRIM52 | Positive regulation of NF-κB signaling | Fan et al. (2017) | ||
| Restriction of flaviviruses | JEV | Ubiquitination and subsequent degradation of viral NS2A protein | Fan et al. (2016b) | |
| TRIM56 | Positive regulation of the STING signaling pathway | K63-linked ubiquitination of STING which facilitates dimerization and TBK1 recruitment | Tsuchida et al. (2010) | |
| Restriction of flaviviruses and coronaviruses | BVDV, YFV, DENV2, hCoV-OC43 | Wang et al. (2011b); Liu et al. (2014) | ||
| Positive regulation of TLR3 signaling pathway | HCV | Shen et al. (2012) | ||
| Restriction of orthomyxoviruses | IAV, IBV | Inhibition of viral RNA synthesis | Liu et al. (2016b) | |
| Restriction of retroviruses | HIV-1 | Kane et al. (2016) | ||
| TRIM59 | Negative regulation of NF-κB and IRF3/7 signaling pathways | Kondo et al. (2012) | ||
| TRIM62 | Restriction of retroviruses and involvement in the TLR4 signaling pathway | N-MLV | Uchil et al. (2013) | |
| TRIM65 | Positive regulator of the MDA5 signaling pathway | ECMV | K63-linked ubiquitination of MDA5, thus promoting MDA5 oligomerization and activation | Lang et al. (2016) |
| TRIM68 | Negative regulation of type I IFN signaling | Polyubiquitination and degradation of TGF which interacts with NEMO | Wynne et al. (2014) | |
| TRIM79α | Restriction of flaviviruses | TBEV | Degradation of the viral RNA polymerase | Taylor et al. (2012) |