Differential Desensitization to Type I Interferons Figure 6. USP18 is sufficient to induce differential desensitization. (A) Level of Stat2 and Stat1 phosphorylation induced by 30 min stimulation with IFN a2 or IFN b in na¨ıve and primed HLLR1-1.4 cells and in clone HU13 stably expressing USP18. Level of USP18 in na¨ıve and primed HLLR1-1.4 cells (endogenous USP18) and in HU13 cells (ectopic USP18). Level of ISG15, a typical ISG, in na¨ıve and primed HLLR1-1.4 and in HU13 cells. Loading was evaluated by measuring AKT. Lysates (30 mg) were immunoblotted with the indicated Abs. (B) Kinetics of Tyk2, Stat1 and Stat2 PLoS ONE | www.plosone.org 8 July 2011 | Volume 6 | Issue 7 | e22200