Measles virus (MeV) is a highly immunotropic and contagious pathogen that can even diminish preexisting antibodies, and remains a major cause of childhood morbidity and mortality worldwide despite the availability of effective vaccines. MeV is one of the most extensively studied viruses with respect to mechanisms of JAK-STAT antagonism. Of the three proteins translated from the MeV P gene, P and V are essential for inactivation of this pathway. However, the lack of data from direct analyses of the underlying interactions means that the detailed molecular mechanism of antagonism remains unresolved. Here we prepared recombinant MeV V protein, which is responsible for human JAK-STAT antagonism, and a panel of variants, enabling the biophysical characterization of V protein including direct V/STAT1 and V/STAT2 interaction assays. Unambiguous direct interaction between the host and viral factors, in the absence of other factors such as Jak1 or Tyk2, were observed and the dissociation constants were quantified for the first time. Our data indicate that interactions between the C-terminal region of V and STAT2 is one order of magnitude stronger than that of the N-terminal region of V and STAT1. We also clarified that these interactions are completely independent of each other. Moreover, results of size-exclusion chromatography demonstrated that addition of MeV-V displaces STAT2-core, a rigid region of STAT2 lacking the N and C-terminal domains, from pre-formed complexes of STAT2-core/IRF-associated-domain (IRF9). These results provide a novel model whereby MeV-V can not only inhibit the STAT2/IRF9 interaction but also disrupt pre-assembled interferon-stimulated gene factor 3. IMPORTANCE To evade host immunity, many pathogenic viruses inactivate host Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways using diverse strategies. Measles virus utilizes P and V proteins to counteract this signaling pathway. Data derived largely from cell-based assays have indicated several amino acid residues of P and V proteins as important. However, biophysical properties of V protein or its direct interaction with STAT molecules using purified proteins have not been studied. We have developed novel molecular tools enabling us to identify a novel molecular mechanism for immune evasion whereby V protein disrupts critical immune complexes, providing a clear strategy by which measles virus can suppress interferon–mediated antiviral gene expression.

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Ceramics have generally been fabricated from powders by shape forming & sintering methods except for glasses and glass ceramics. Glasses and glass ceramics can be fabricated by melting methods. The melting method has not only higher productivity but also higher shape forming ability than powder processes via forming & sintering methods. Thus we have reinvestigated melting methods in binary and ternary oxides systems to fabricate amorphous bulk ceramics and bulk nano composites. We have successfully fabricated amorphous phases by simple melt solidification methods in ternary eutectic melts in the HfO 2 -Al 2 O 3 -Gd 2 O 3 system. The present study demonstrates the formation of the amorphous phases in quaternary systems HfO 2 -Al 2 O 3 -Gd 2 O 3 -Eu 2 O 3 . Furthermore, we have also succeeded to fabricate nanostructured bulk ceramics, which consisted of constituent oxide grains with 20-100 nm in size, by post annealing of the amorphous phase.

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