Figure 6.

TRIM21 deficient mice increases CVB3 replication in organs and aggravates pancreatic acinar cell necrosis as well as myocarditis. (A) Schematic diagram of deficient mice construction by CRISPR-CAS9 strategy. (B,C) Q-PCR and Western blot analysis of TRIM21 expression from tissues and BM cells of wild-type (WT) and TRIM21-/- mice, GAPDH was used as a loading control. (D-H) WT and TRIM21-deficient mice were infected i.p. with CVB3 (n = 6).The body weight change were monitored daily until day 7 p.i. (D). Representative image of HE-staining hearts and pancreas of CVB3-infected WT or TRIM21-/-mice (day 7 p.i.), showing intra-cardiac immune infiltrates or intactpancreatic acini (marked with arrows). Scale bar: 100 μm. Pathological scores of the heart and pancreas of mice are shown. Results are presented as mean ± SEM; Data pooled from 3 independent experiments (E).The mRNA levels of inflammatory cytokines in the homogenates of heart (day 7 p.i.) were measured by Q-PCR. Data were presented as mean ± SEM of three representative independent (F).Viral loadin pancreas and hearts of mice(day 3p.i.) was assessed by TCID₅₀ assay. Results are presented as mean ± SEM;Data pooled from 3 independent experiments. *p < 0.05; **p < 0.01 (G).The mRNA and protein level of IFN-β (day 1–3 p.i.) in hearts of mice was detected by Q-PCR and ELISA. Data as mean ± SEM of three representative independent. *p < 0.05; **p < 0.01 (H). (I) Proposed model depicting the role of TRIM21 in positive regulation of IFN-I production during CVB3 infection. TRIM21 targets and promotes the activity of MAVS, leading to the increased phosphorylation and translocation of p-IRF3 into the nucleus, leading to enhanced transcription and production of IFNs and IFN-stimulated genes (ISGs) that limits CVB3 infection.