Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants.
Int J Cancer
; 110(1): 15-21, 2004 May 20.
Article
em En
| MEDLINE
| ID: mdl-15054864
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.
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Base de dados:
MEDLINE
Assunto principal:
Orthomyxoviridae
/
Interferons
/
Proteínas não Estruturais Virais
/
Neoplasias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article