I have a strong interest in understanding the molecular mechanism of innate antiviral response. Previously, our laboratory has illustrated that a major cellular pattern recognition receptor (PRR) named RIG-I, which plays an important role in innate immunity and serves as the primary sensor of viral RNAs in the cytoplasm, requires a double-stranded RNA binding partner known as PACT for optimal activation by viral RNA (Kok et al., 2011). PACT potently activates RIG-I-mediated type I interferon production during the course of Sendai virus infection. The effect of PACT on another viral RNA sensor, MDA5, was also investigated in encephalomyocarditis virus-infected cells. These findings support our model that the recognition of different viral RNAs by RIG-I and MDA5, requires host cell double-stranded RNA binding protein PACT.

In connection to this, I have tried to understand virus-host interaction during the course of viral infection. The key question that I want to tackle is how viruses counteract innate immune response and escape from the action of cellular PRRs. To facilitate viral replication, most animal viruses employ different strategies to dampen host innate immunity. Recently, we have demonstrated that herpes simplex virus 1 Us11 protein robustly suppresses the activation of PACT- and RIG-I-mediated interferon production (Kew et al. , 2013). In addition, we have also reported severe acute respiratory syndrome coronavirus M protein (Siu et al., 2014) and Middle East respiratory syndrome coronavirus 4a protein (Siu et al., 2014) as suppressors of innate antiviral response. Besides, we have also characterized how hepatitis B virus makes use of the cellular transcription coactivator CRTC1 to facilitate viral transcription (Tang et al., 2014). One of my ongoing projects aims to understand the roles of Influenza A virus NS1 protein in viral replication and innate antiviral response evasion. I am interested in dissecting the molecular pathways involved.

The next step of my research development is to integrate mechanistic study of innate immunity with translational medicine. Further dissection of viral evasion mechanisms against antiviral response and elucidation of how PACT and RIG-I/MDA5 recognize various viral RNAs will not only derive new knowledge in molecular virology and immunology, but may also provide the foundation for future design and development of antivirals, immunomodulatory agents and vaccine adjuvants.