title: Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants.
abstract: NS1 protein of influenza virus is a virulence factor that counteracts Type I interferon (IFN)-mediated antiviral response by the host. A recombinant influenza A virus that lacks the NS1 protein only replicates efficiently in systems that contain defective IFN pathways. We demonstrate that the conditional replication properties of NS1-modified influenza A virus mutants can be exploited for the virus-mediated oncolysis of IFN-resistant tumor cells. IFN resistance in analyzed tumor cell lines correlated with a reduced expression of STAT1. Addition of exogenous IFNalpha or supernatant of virus-infected endothelial cells inhibited viral oncolysis in IFN-sensitive but not in IFN-resistant cell lines. The oncolytic potential of NS1-modified influenza A virus mutants could be exploited in vivo in a SCID mouse model of a subcutaneously-implanted human IFN-resistant melanoma. The data indicate that IFN-resistant tumors are a suitable target for oncolysis induced by NS1-modified influenza virus mutants. STAT1 might serve as a marker to identify these IFN-resistant tumors.
authors.affiliation: Department of Dermatology, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Muster
authors.forename: Julia
authors.initials: J
authors.lastname: Rajtarova
authors.forename: Monika
authors.initials: M
authors.lastname: Sachet
authors.forename: Hermann
authors.initials: H
authors.lastname: Unger
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fleischhacker
authors.forename: Ingrid
authors.initials: I
authors.lastname: Romirer
authors.forename: Andreas
authors.initials: A
authors.lastname: Grassauer
authors.forename: Angelika
authors.initials: A
authors.lastname: Url
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Klaus
authors.initials: K
authors.lastname: Wolff
authors.forename: Hubert
authors.initials: H
authors.lastname: Pehamberger
authors.forename: Michael
authors.initials: M
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D017353:Gene Deletion; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy* / Q000821:virology; D009975:Orthomyxoviridae / Q000235:genetics*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000032:analysis; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; C085820:INS1 protein, influenza virus; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D017361:Viral Nonstructural Proteins; D007372:Interferons