IndraLab

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USP18 activates IFNA. 17 / 17
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"In the current study, for the first time, we demonstrated that ISG15 and USP18 protein levels are increased in HCV infected PHHs and IFN-lambda4-expressing or -treated cells and that ISG15 and USP18 proteins mediate IFN-alpha unresponsiveness in IFN-lambda4-expressing or -treated cells."
28630501
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"Taken together, we concluded that USP18 potentiates the anti-HBV activity of IFN-alpha by targeting the JAK and STAT signaling pathway in Hepg2.2.15 cells."
27227879
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"Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-alpha, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-alpha refractory state, which was reversed by USP18 knockdown."
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"Overexpression of USP18 promoted DENV-2 replication, while its silencing abrogated the replication and increased the anti-DENV-2 specific IFN-α through the activation of the IFN-α-mediated Jak/STAT signaling pathway, as shown by the increased expression of p-STAT1/p-STAT2 and the elevated expression of some ISGs."
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"In addition, lacking USP18 can abrogated the refractory status induced by IFN-alpha stimulation, which indicates that lack of USP18 in the Hepg2.2.15 cells could enhance the antiviral activity of IFN-alpha (XREF_SUPPLEMENTARY)."
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"Namely, free extracellular ISG15 is crucial in IFN-gamma-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18 mediated downregulation of IFN-alpha and beta signalling."
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"The ISG15 and USP18 mediated IFN-alpha unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18."
28630501
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"In the absence of ISG15, USP18 proteolysis is more rapid, driving the dysregulated IFN-alpha and beta response and resulting in both the blood IFN-alpha and beta signature and brain calcifications seen in the patients."
25307056
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"Extracellularly, the ISG15 protein is essential for IFN-gamma-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-alpha/beta signalling."
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"Our results indicated that USP18 modulates the anti-HBV activity of IFN-alpha via activation of the JAK and STAT signaling pathway in Hepg2.2.15 cells."
27227879
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"Furthermore, previous studies reported that blocking of IFN-alpha signaling by USP18 does not depend on the enzymatic activity of USP18 27."
28630501
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"In cell culture, siRNA mediated depletion of USP18 enhanced ISG induction as well as the antiviral effect of IFN-alpha against HCV replication."
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"The IFN-alpha signal blocking activity of USP18 is mediated by the binding of USP18 to the intracellular domain of IFNAR2, which prevents the binding of JAK1 to IFNAR2 27."
28630501
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"Usp18 deficient cells have enhanced IFN-alpha and beta signaling and more ISG15 modified proteins."
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"Furthermore, USP18 promotes HCV and HBV replication by specifically inhibiting IFN-α and utilizing the IFN stimulated gene 15 (ISG15)/USP18 pathway, as well as fostering a cellular environment characterized by CD81 upregulation and promoting viral entry and infectivity (87, 88)."
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"These results collectively suggested that silencing USP18 activated IFN-alpha signaling, JAK and STAT signaling, in a prolonged fashion."
27227879
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"Leading edge analysis showed that, as compared to treated cells, untreated cells were enriched in NF‐κB pathway genes but ‘IFNA response’ genes including type I IFN genes ISG15, IFIT2, IFIT3, MX1 and USP18 41 were induced by DMX3433 treatment.4 DISCUSSION."
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