Inhibition of FTO activity enhances KSHV lytic gene expression, while blocking of m6A abolishes lytic gene expression and virion production. (A and B) Relative levels of KSHV latent transcripts (5.4 kb and 5.8 kb) and lytic transcripts ORF50 (RTA) and ORF57 in BCBL1 cells treated with PBS (control), MA (1 μM), DAA (25 μ), and TPA, alone or in combination, for 24 h. (C) Levels of m6A-mRNA of ORF50 (RTA) and ORF57 in the BCBL1 cells described in the legend to panels A and B. (D) Western blot detection of KSHV latent protein LANA (ORF73) and lytic proteins encoded by ORF50 (RTA), ORF57, ORF62, and ORF65 in cells treated as described in the legend to panels A and B for 24 h and 72 h. (E) Representative images of HUVECs at 72 h postinfection with culture supernatants from equal numbers of BCBL1-BAC36 cells that were stimulated as described in the legend to panels A and B and collected at 5 days after treatment. (F) Percentage of GFP-positive cells at 72 h postinfection with the different culture supernatants described in the legend to panel E.