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. 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). 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 TP53 signaling pathway. Interacts with host TP53 and prevents its interaction with the deubiquitinase USP7, leading to sequestration of TP53 in the host cytoplasm thereby diminishing its transcriptional activity (PubMed:34523970). Interacts with host IRF7 (PubMed:11943871). Interacts with host RPS6KA1 (PubMed:30842327). Interacts with host RAB11FIP5; this interaction results in the lysosomal degradation of ORF45 and the inhibition of viral particle release (PubMed:33315947). Interacts with host TP53; this interaction down-regulates TP53 signaling pathway (PubMed:34523970). Phosphorylated on Ser-41 and Ser-162 by host IKBKE and TBK1.