ADAR1 edits MeV genomes and is required for efficient viral replication.

(A and B) Growth curve analyses of (A) MeV-vac2(GFP) and (B) MeV-CKO(GFP) in HeLa cell lines infected at an MOI of 0.1 and harvested at the time points indicated. Values are average ± standard deviation of n = 5 for each time point. For p150KO cells, 3 replicates were generated on clone B13 and 2 replicates on clone C10. For ADAR1KO cells, 3 replicates were generated on clone E7 and 2 replicates on clone E2. Significance was determined by unpaired two-tailed Student’s t test and is indicated with asterisks (*, P P S1 Data. (C) Absolute number of viral reads with >5 mutations (“NM>5”) in RNAseq samples. Underlying values can be found in S1 Data. (D) Frequency of these reads relative to total number of MeV-specific reads. U>C: reads with predominantly U>C mutations (red); A>G: reads with predominantly A>G mutations (green). Underlying values can be found in S1 Data. (E) Editing scores of MeV-vac2(GFP) and MeV-CKO(GFP) genomes from HeLa, p150KO, and ADAR1KO infections. Scores are shown for transitions (A>G, green; U>C, red; G>A, orange; C>U, blue) and a read coverage (gray) of at least 10. (F and G) Correlation of (F) MeV-vac2(GFP) and (G) MeV-CKO(GFP) genome editing between HeLa and p150KO cells (gray dots and black line) or HeLa and ADAR1KO cells (red dots and line). ADAR1, adenosine deaminase acting on RNA 1; ADAR1KO, fully ADAR1-deficient; KO, knock-out; lin. regr., linear regression; MeV, measles virus; MOI, multiplicity of infection; NT, nucleotide; p150KO, selectively ADAR1p150-deficient; RNAseq, RNA sequencing.