Transcription profiling by array of human malignant peripheral nerve sheath tumor cells after infection with herpes simplex virus G207

We used microarrays to identify genes regulated during oncolytic HSV infection. Oncolytic herpes simplex viruses (oHSV) are promising anticancer therapeutics. We sought to identify alterations in gene expression during oHSV infection of human cancer cells. Human malignant peripheral nerve sheath tumor (MPNST) cells were infected with G207, an ICP34.5-deleted oHSV previously evaluated in clinical trials. G207-infected cells demonstrated massive degradation of cellular mRNAs, while a subset were upregulated. A gene signature of 21 oHSV-induced genes contained 7 genes known to be HSV-induced. Go ontology classification revealed that a majority of upregulated genes are involved in Jak/STAT signaling, transcriptional regulation, nucleic acid metabolism, protein synthesis and apoptosis. Ingenuity-defined functional networks highlighted nodes for AP-1 subunits and interferon signaling via STAT1, SOCS1, SOCS3 and RANTES. Upregulation of SOCS1 correlated with sensitivity of MPNST lines to G207 and depletion of SOCS1 reduced virus replication >1-log. The transcriptome of oHSV-induced genes may predict oncolytic efficacy and provides rationale for next generation oncolytics. Experiment Overall Design: 5 human MPNST cancer cell lines were infected with G207 or mock infected for 6 hours followed by RNA extraction and hybridization on Affymetrix microarrays.