University of Rijeka

About: University of Rijeka is a education organization based out in Rijeka, Croatia. It is known for research contribution in the topics: Population & Tourism. The organization has 3471 authors who have published 7993 publications receiving 110386 citations. The organization is also known as: Rijeka University & Sveučilište u Rijeci.

A cytomegaloviral protein reveals a dual role for STAT2 in IFN-γ signaling and antiviral responses

Abstract: A mouse cytomegalovirus (MCMV) gene conferring interferon (IFN) resistance was identified. This gene, M27 , encodes a 79-kD protein that selectively binds and downregulates for signal transducer and activator of transcription (STAT)-2, but it has no effect on STAT1 activation and signaling. The absence of pM27 conferred MCMV susceptibility to type I IFNs ( � / � ), but it had a much more dramatic effect on type II IFNs ( � ) in vitro and in vivo. A comparative analysis of M27 � and M27 � MCMV revealed that the antiviral efficiency of IFN- � was partially dependent on the synergistic action of type I IFNs that required STAT2. Moreover, STAT2 was directly activated by IFN- � . This effect required IFN receptor expression and was independent of type I IFNs. IFN- � induced increasing levels of tyrosine-phosphorylated STAT2 in M27 � MCMV-infected cells that were essential for the antiviral potency of IFN- � . pM27 represents a new strategy for simultaneous evasions from types I and II IFNs, and it documents an unknown biological significance for STAT2 in antiviral IFN- � responses.

NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145

Abstract: The NK cell-activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. Screening a panel of MCMV deletion mutants defined the gene m145 as the viral regulator of MULT-1. The MCMV m145-encoded glycoprotein turned out to be necessary and sufficient to regulate MULT-1 by preventing plasma membrane residence of MULT-1. The importance of MULT-1 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 deletion that was lifted after NK cell depletion. Our findings underline the significance of escaping MULT-1/NKG2D signaling for viral survival and maintenance.