P122 Dengue virus targets the adaptor protein MITA to subvert host innate immunity
Introduction The pathogenesis of severe dengue diseases remains unclear, but magnitude of dengue virus (DEN) replication is believed to be one of the major determining factors. Thus, revealing how DEN evades the host defense mechanism such as type I interferon (IFN) system is important for better understanding this devastating disease. Although several DEN viral proteins have been reported as IFN-resistant factors, without knowing the cellular targets, the mechanism of how DEN subverts IFN system is poorly understood. Methods We performed DEN infection in stable cell lines with manipulated expression of host factor MITA/MPYS by overexpression or RNAi knockdown. Results We found that the human mediator of IRF3 activation (MITA), also known as STING and ERIS, was cleaved in cells infected with DEN and in cells expressing an enzymatically active DEN protease NS2B3. MITA is known as a DNA sensor for IFN production and its antiviral role has also been demonstrated for several DNA and RNA viruses. DEN protease appears to cleave MITA but not its murine homologue MPYS, and this cleavage resulted in impaired MITA activation. Ectopic overexpression of MPYS but not MITA reduced DEN replication, and knockdown of endogenous MPYS enhanced DEN replication. Conclusion MITA/MPYS is involved in host defense against DEN replication and DEN protease targets MITA to subvert its antiviral effect.