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Interferon resistance promotes oncolysis by influenza virus NS1‐deletion mutants
Author(s) -
Muster Thomas,
Rajtarova Julia,
Sachet Monika,
Unger Hermann,
Fleischhacker Reinhard,
Romirer Ingrid,
Grassauer Andreas,
Url Angelika,
GarcíaSastre Adolfo,
Wolff Klaus,
Pehamberger Hubert,
Bergmann Michael
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20078
Subject(s) - oncolytic virus , virology , virus , interferon , biology , influenza a virus , cell culture , mutant , stat1 , orthomyxoviridae , viral replication , gene , biochemistry , genetics
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 IFNα 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. © 2004 Wiley‐Liss, Inc.