Figure 3. Evasion of PRR-mediated recognition, signalling and gene expression by herpesviruses.
The HSV proteins ICP34.5 and Vhs prevent the recognition of viral nucleic acids by inhibiting autophagy and degrading viral RNA, respectively. Herpesviruses inhibit signaling through both PRR-specific mechanisms (HSV-1 ICP0 inhibits TLR2 signalling by stimulating degradation of TLR adaptor molecules, and MCMV M45 inhibits recruitment or RIP1 to DAI) and more general mechanisms targeting all PRRs (for example, HHV8 ORF45 interacts with IRF7 and inhibits phosphorylation and nuclear translocation). Finally, several herpesvirus-encoded proteins (such as HHV8 vIRF3) inhibit transcription by interacting with NF-κB and IRF3 and/or IRF7 in the nucleus, hence preventing interaction with DNA and assembly of functional transcriptional complexes. CMV, cytomegalovirus; DAI, DNA-dependent activator of interferon regulatory factors; HHV, human herpesvirus; ICP, infected cell protein; IRF, interferon regulatory factor; NF, nuclear factor; ORF, open reading frame; PRR, pattern recognition receptor; RIP, receptor-interacting protein kinase; TLR, Toll-like receptor; Vhs, virion host shut-off.