Virus-STAT Interactions: Roles in Disease and Therapeutic Targeting
Viral evasion of interferon (IFN)-mediated immunity is critical to infection and depends on interactions of viral IFN-antagonist proteins with STATs, essential mediators of IFN signaling.
Using live-cell imaging, immune antagonism assays, and viral reverse genetics/disease models, we identified novel interactions of IFN-antagonists with STAT family members, and developed specific inhibitory mutations to demonstrate critical roles in infection in vivo (Figure 1) and disease progression, forming the basis of a novel vaccine approach.
Using these unique tools, and techniques including genomics/proteomics, crystallography/NMR, and dynamic live-cell imaging, projects aim to define the mechanisms of action of IFN/STAT antagonists in diseases caused by viruses such as rabies and Hendra, and to characterise virus-STAT interactions as targets for vaccine/antiviral drug development.
Figure 1: Titration of rabies virus in the central nervous system of mice infected with wild-type (WT) or mutant virus lacking STAT antagonist function (STAT(-)) reveals significant attenuation of the mutant virus.
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