The polyoma virus T antigen interferes with interferon-inducible gene expression.
Murine polyoma virus (MPyV) is a small DNA virus that induces tumors in multiple tissues of infected host. In this investigation, we show that cell lines derived from wild type virus-induced breast tumors are resistant to the growth inhibitory action of interferon beta (IFN-beta). Furthermore, replication of heterologous viruses such as vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by IFN-beta in these cells. This effect was due to inhibition of IFN-stimulated gene expression by viral T antigen. Activation of IFN-stimulated gene factor 3 was inhibited in cells derived from a tumor induced by wild-type MPyV but not those from a mutant that lacks the pRB binding site of the large T antigen. Similarly IFN-gamma-inducible gene expression was also inhibited in cells transformed by wild-type virus. The levels of components of IFN-stimulated gene factor 3 and signal transducing Janus tyrosine kinases were comparable between the cells transformed by the wild-type and mutant viruses. The viral large T antigen bound to Janus tyrosine kinase 1 and inactivated signaling through IFN receptors. Thus, these studies identify a mechanism of viral resistance to IFN action.
Weihua
X
X
Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ramanujam
S
S
Lindner
D J
DJ
Kudaravalli
R D
RD
Freund
R
R
Kalvakolanu
D V
DV
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D002472:Cell Transformation, Viral; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004686:Encephalomyocarditis virus / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D053613:Janus Kinase 1; D051379:Mice; D011120:Polyomavirus / Q000276:immunology / Q000502:physiology*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D014157:Transcription Factors; D016899:Interferon-beta; D007371:Interferon-gamma; D004247:DNA; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1