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, A standard protocol according to manufacturer's instructions was followed. The following protocol refers to the use of 96-well plates. 180 mL of QUANTI-Blue Solution was dispensed per well into a flat-bottom 96-well plate. 20 mL of sample (supernatant of SEAP-expressing cells) or negative control (cell culture medium) were added and incubated at 37 C for 15 min to 6 h. Optical density (OD) at 620nm was measured using a microplate reader, Quanti-blue SEAP Phosphatase assay QUANTI-blue Gold is a two-component kit which contains: -QB reagent and -QB buffer, provided by Invivogen (HK)

;. Quanti-luc-luciferase-assay-quanti-luc, -. Quanti-luc-plus, . Fbs, 1. 1%-p/s, and . Hepes, Transfection was carried out with TransIT reagent, following the manufacturer's instructions. Plasmids VSV-G, PLP1 (GAG/POL), PLP2 and plenti vector (plasmid of interest) were co-transfected with TransIT reagent in Opti-MEM. 24h after transfection, the supernatant was removed with a syringe, filtered on 0.22mm and stored overnight at À80 C. Virus particles collected from supernatants were concentrated by ultracentrifugation (28000 rpm, 4 C). Pellets were resuspended in 100 ml of PBS and left at 4 C for 1h to resuspend the virus. A549 cells were seeded in 10 cm dish with a density of 4 3 10 6 cells/dish before lentiviral transduction. Transduction was performed using 30 ml of virus/dish (with dropwise distribution). 2 days after, the medium was changed and supplemented with 5 mg/ml of blasticidin. Medium was replaced every three days and selection pressure was kept for two weeks, Quanta-Luc pouches were distransfected using either Fugene6 (Roche Diagnostics), vol.12

. Sanyal, At appropriate time points, aliquots were withdrawn and the reaction was stopped with cold PBS. Cell pellets were lysed in Tris buffer containing TX-100 and pre-cleared with agarose beads for 1 hour at 4 C. Immunoprecipitations were performed for 3h at 4 C with gentle agitation. Samples were eluted by boiling in reducing sample buffer, subjected to SDS-PAGE and visualized by autoradiography, 2013.

. Mali, After 3 days, medium was replaced with that without puromycin and selected cells were allowed to grow for 1-2 weeks depending on the number of surviving cells. Deletion efficiency was checked in the mixed populations. For clonal expansion, selected cells were seeded in a 10 cm dish at a low density of 20 cells/dish. Pyrexâ 8mm cloning cylinders were used to demarcate single colonies and silicone grease was used to create an isolated well, 2013.

. Zeng, 10 mM KCl, 1.5 mM MgCl 2 , 0.5 mM EGTA, and protease inhibitor cocktail] was used to prepare cytosol fractions, and isotonic buffer (hypotonic buffer plus 0.25 M D-Mannitol) was used to prepare mitochondrial membranes. Cells were homogenized in appropriate buffers, and centrifuged at 600 g for 5 minutes to pellet nuclei. Post-nuclear supernatants were further centrifuged at 10,500 x g for 10 minutes to collect mitochondrial membranes in the pellet fraction. Supernatants were subjected to centrifugation at 100,000 g, to separate cytosol fractions from microsomes. Pelleted mitochondrial membranes were washed once with isotonic buffer. For IRF3 pathway activation by RIG-I, the reaction mixture contained 1 mg/ml mitochondrial prep, 3 mg/ml cytosol fractions (from OTUB1-deficient cells expressing OTUB1 variants), 1xMgATP buffer, In vitro reconstitution of IRF3 dimerization Biochemical assays for IRF3 activation with cytosolic extracts and mitochondrial preparations were as described previously, 2010.