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. 2020 Mar 2;11:1146. doi: 10.1038/s41467-020-14948-z

Fig. 8. STAT1-K511/652 mutation enhances IFN-I antiviral activity.

Fig. 8

a Diagram of bone marrow chimeras using wild-type BALB/c mice as recipients and Stat1−/− (129S6) mice as donors. b The bone marrow was obtained from BALB/c mice that were irradiated and injected (i.v.) with the Stat1−/− bone marrow with lentiviral packaging GFP-STAT1 (WT or K511/652 R), followed by administration with mIFNβ (1500 IU/g, i.p.) for 8 h. Immunoprecipitation and western blot were performed to analyze pY701-STAT1 and GFP-STAT1 levels. c RT-qPCR analysis of the representative ISGs (Ifit1 and Rsad2) mRNA in the bone marrow from recipient mice treated as b. d Linear ubiquitination of STAT1 restricts the interaction between STAT1 and IFNAR2, thus inhibiting STAT1 activation and maintaining homeostasis of IFN signaling. Viral infection rapidly induces production of IFNs, which utilize OTULIN to remove linear ubiquitination of STAT1, thus promoting STAT1 activation. During the late stage of viral infection, HOIP expression is upregulated through the NF-κB signaling pathway, which increases STAT1 linear ubiquitination and inhibits host IFN antiviral response. ***p < 0.001 (two-tailed unpaired Student’s t test). All graphs show the mean ± SEM for six individual mice (c). Data are representative of three independent experiments (b).