TRIM11 Negatively Regulates IFNβ Production and Antiviral Activity by Targeting TBK1

<div><p>The innate immune response is a host defense mechanism against infection by viruses and bacteria. Type I interferons (IFNα/β) play a crucial role in innate immunity. If not tightly regulated under normal conditions and during immune responses, IFN production can become aberrant, leading to inflammatory and autoimmune diseases. In this study, we identified TRIM11 (tripartite motif containing 11) as a novel negative regulator of IFNβ production. Ectopic expression of TRIM11 decreased IFNβ promoter activity induced by poly (I:C) stimulation or overexpression of RIG-I (retinoic acid-inducible gene-I) signaling cascade components RIG-IN (constitutively active form of RIG-I), MAVS (mitochondrial antiviral signaling protein), or TBK1 (TANK-binding kinase-1). Conversely, TRIM11 knockdown enhanced IFNβ promoter activity induced by these stimuli. Moreover, TRIM11 overexpression inhibited the phosphorylation and dimerization of IRF3 and expression of IFNβ mRNA. By contrast, TRIM11 knockdown increased the IRF3 phosphorylation and IFNβ mRNA expression. We also found that TRIM11 and TBK1, a key kinase that phosphorylates IRF3 in the RIG-I pathway, interacted with each other through CC and CC2 domain, respectively. This interaction was enhanced in the presence of the TBK1 adaptor proteins, NAP1 (NF-κB activating kinase-associated protein-1), SINTBAD (similar to NAP1 TBK1 adaptor) or TANK (TRAF family member-associated NF-κB activator). Consistent with its inhibitory role in RIG-I-mediated IFNβ signaling, TRIM11 overexpression enhanced viral infectivity, whereas TRIM11 knockdown produced the opposite effect. Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex.</p></div

La Croix du Nord : supplément régional à la Croix de Paris ["puis" grand journal quotidien du Nord de la France]

05 août 19111911/08/05 (A22,N7581).Appartient à l’ensemble documentaire : NordPdeC

Additional file 21: Figure S8. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

Same directional gene expression changes across tissues in the adult female Duroc and validation datasets. Expression differences of the 10 most up- and downregulated genes between each tissue comparison from the adult female Duroc compared to the differences observed for the same genes in the validation dataset. a Log2 fold change differences in expression between liver and spleen, b liver and muscle, and c spleen and muscle. d Correlation between log2 fold changes in the adult female Duroc and validation dataset for all 3 tissue comparisons. (PNG 9535 kb

Additional file 20: Table S13. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

GO terms and KEGG pathways enriched for ASE. (XLSX 10 kb

Additional file 2: Table S2. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

Validation dataset RRBS and RNA-seq read depths. (XLSX 8 kb

Additional file 16: Figure S4. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

Positive correlation between gene body CpG methylation and gene expression in all tissues. CpG methylation levels in relation to gene expression across gene bodies for a fat, b heart, c kidney, d liver, e lung, f lymph node, g muscle, and h spleen. X axis represents distances in bp. (PNG 15591 kb

Additional file 4: Table S3. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

CpG site coverage and methylation level in relation to genomic features. * denotes percent of sites covered out of total in size fraction. (XLSX 11 kb

Additional file 10: Table S8. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

Methylation level, proportion unmethylated, and methylated (>10 %) CpG sites across chromosomes in male validation dataset. (XLSX 11 kb

Additional file 9: Table S7. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

Proportion of methylated (>10 %) CpG sites across chromosomes. (XLSX 11 kb

Additional file 7: Table S5. of Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

CpG methylation level across chromosomes. (XLSX 10 kb