A Cytomeglaoviral Protein Reveales a Dual Role for STAT2 in IFN-g Signaling and Antiviral Responses

A mouse cytomegalovirus (MCMV) gene conferring interferon (IFN) resistance was identified. This gene, M27, encodes a 79 kDa protein which is selcetively binding and down-regulating STAT2 but has no effect on STAT1 activation and signaling. The absence of pM27 conferred MCMV susceptibility to type I IFNs (a/b) but had a much more dramatic effect to type II IFN (g) in vitro and in vivo. Comparative analysis of M27+ and M27- MCMV revealed that the antiviral efficiency of IFN-g was partially dependent on the synergistic action of type I IFNs which required STAT2. Moreover, STAT2 was directly activated by IFN-g. This effect required IFNGR expression and was independent of type I IFNs. IFN-g induced incerasing levels of tyrosine-phosphorylated STAT2 in M27- MCMV infected cells which were esential for the antiviral potency of IFN-g. pM27 represents a new strategy for simultaneous evasion from type I and type II IFN and documents a hitherto unknown biological significance of STAT2 in antiviral IFN-g responses