THE POLYOMA-VIRUS T-ANTIGEN INTERFERES WITH INTERFERON-INDUCIBLE GENE-EXPRESSION

Murine polyoma virus (MPyV) is a small DNA virus that induces tumors i n multiple tissues of infected host. In this investigation, we show th at cell lines derived from wild type virus-induced breast tumors are r esistant to the growth inhibitory action of interferon beta (IFN-beta) . Furthermore, replication of heterologous viruses such as vesicular s tomatitis virus and encephalomyocarditis virus was not inhibited by IF N-beta in these cells. This effect was due to inhibition of IFN-stimul ated gene expression by viral T antigen. Activation of IFN-stimulated gene factor 3 was inhibited in cells derived from a tumor induced by w ild-type MPyV but not those from a mutant that lacks the pRB binding s ite of the large T antigen, Similarly IFN-gamma-inducible gene express ion was also inhibited in cells transformed by wild-type virus, The le vels of components of IFN-stimulated gene factor 3 and signal transduc ing Janus tyrosine kinases were comparable between the cells transform ed by the wild-type and mutant viruses, The viral large T antigen boun d to Janus tyrosine kinase 1 and inactivated signaling through IFN rec eptors. Thus, these studies identify a mechanism of viral resistance t o IFN action.