Figure 2.

Inhibition of cytoplasmic PRRs by tumour viruses. Cytosolic double-stranded RNA is detected by the RLRs RIG-I and MDA5. RIG-I ubiquitination is inhibited by KSHV ORF64, and RIG-I signalling is inhibited by the HBV polymerase. RLRs signal through the adaptor protein MAVS, which is inhibited by HBV X and the HCV protease. Cytosolic DNA is detected by a variety of DNA sensors, including cGAS. Binding of DNA to cGAS is inhibited by KSHV ORF52 and EBV ORF52. cGAS activity is inhibited by KSHV ORF52, KSHV LANA and HPV E7. DNA sensors activate STING. STING ubiquitination is inhibited by the HBV polymerase, KSHV vIRF1 prevents STING association with TBK1, and HCV NS4B disrupts STING signalling complexes. The NLRP1 inflammasome is inhibited by KSHV ORF63, and HPV E6 mediates degradation of pro-IL-1β.