Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants

Thomas Muster; Julia Rajtarova; Monika Sachet; Hermann Unger; Reinhard Fleischhacker; Ingrid Romirer; Andreas Grassauer; Angelika Url; Adolfo García-Sastre; Klaus Wolff; Hubert Pehamberger; Michael Bergmann

doi:10.1002/ijc.20078

Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants

Thomas Muster, Julia Rajtarova, Monika Sachet, Hermann Unger, Reinhard Fleischhacker, Ingrid Romirer, Andreas Grassauer, Angelika Url, Adolfo García-Sastre, Klaus Wolff, Hubert Pehamberger, Michael Bergmann

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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 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.

Original language	English
Pages (from-to)	15-21
Number of pages	7
Journal	International Journal of Cancer
Volume	110
Issue number	1
DOIs	https://doi.org/10.1002/ijc.20078
State	Published - 20 May 2004

Keywords

Conditionally-replicating-virus
SCID
STAT1

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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 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.",

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AU - Muster, Thomas

AU - Rajtarova, Julia

AU - Sachet, Monika

AU - Unger, Hermann

AU - Fleischhacker, Reinhard

AU - Romirer, Ingrid

AU - Grassauer, Andreas

AU - Url, Angelika

AU - García-Sastre, Adolfo

AU - Wolff, Klaus

AU - Pehamberger, Hubert

AU - Bergmann, Michael

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N2 - 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.

AB - 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.

KW - Conditionally-replicating-virus

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KW - STAT1

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EP - 21

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 1

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Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants

Abstract

Keywords

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