KSHV ORF45

KSHV ORF45

Prevents the establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of host interferon regulatory factor 7/IRF7, a transcription factor critical for the induction of interferons alpha and beta (PubMed:11943871, PubMed:20485504, PubMed:22787218).
Mechanistically, ORF45 competes with the associated IRF7 and inhibits its phosphorylation by IKBKE or TBK1 by acting as an alternative substrate (PubMed:11943871, PubMed:22787218).
Acts as an activator of the NLRP1 inflammasome via interaction with the N-terminal part of host NLRP1: interaction promotes translocation of the N-terminal part of NLRP1 into the nucleus, relieving autoinhibition of the NLRP1 inflammasome and leading to its activation (PubMed:35618833).
Also plays a role in promoting the late transcription and translation of viral lytic genes by constitutively activating host extracellular signal-regulated kinase (ERK)-p90 ribosomal S6 kinase/RPS6KA1 (PubMed:30842327).
In addition, supports the viral replication cycle by modulating host p53/TP53 signaling pathway (PubMed:34523970).
Interacts with host p53/TP53 and prevents its interaction with the deubiquitinase USP7, leading to sequestration of P53/TP53 in the host cytoplasm thereby diminishing its transcriptional activity (PubMed:34523970).

Symbiont-mediated perturbation of host innate immune response
Symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity

Virion tegument
Host cytoplasm
Host nucleus
Host Golgi apparatus

Phosphorylated on Ser-41 and Ser-162 by host IKBKE and TBK1.