A Cytomeglaoviral Protein Reveales a Dual Role for STAT2 in IFN-g Signaling and Antiviral Responses (CROSBI ID 112822)
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Zimmermann, Albert ; Trilling, Mirko ; Wagner, Markus ; Wilborn, Manuel ; Bubić, Ivan ; Jonjić, Stipan ; Koszinowski, Ulrich ; Hengel, Hartmut
engleski
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.
Cytomegalovirus; IFN-g; STAT; immune evasion
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