Δγ134.5 Herpes Simplex Viruses Encoding Human Cytomegalovirus IRS1 or TRS1 Induce Interferon Regulatory Factor 3 Phosphorylation and an Interferon-Stimulated Gene Response

The chimeric herpes simplex viruses (HSV) are Delta gamma(1)34.5 vectors encoding the human cytomegalovirus (HCMV) IRS1 or TRS1 genes. They are capable of late viral protein synthesis and are superior to Delta gamma(1)34.5 HSVs in oncolytic activity. The interferon (IFN) response limits efficient HSV gene expression and replication. HCMV TRS1 and IRS1 restore one gamma(1)34.5 gene function: evasion of IFN-inducible protein kinase R, allowing late viral protein synthesis. Here we show that, unlike wild-type HSV, the chimeric HSV do not restore another gamma(1)34.5 function, the suppression of early IFN signaling mediated by IFN regulatory factor 3 (IRF3).