The overall research focus of our lab is to answer the important question of how coronaviruses cause disease. We aim to address this question by dissecting and understanding the process of pathogenesis and disease progression after coronavirus infection. We use various virology and immunology approaches to investigate virus- and immune (host)-mediated pathogenesis in various model systems. We are particularly interested in coronavirus-host interactions and how these interactions affect overall disease outcome. Another major direction of our lab is to develop cell and animal models for coronavirus infection. Robust and reliable models are not only critical to answer basic scientific questions but also essential for vaccine and antiviral development.
Areas of CoV pathogenesis of interests to the Wong lab
Coronaviruses encode three groups of proteins which are important for their life cycle. Although the functions of most viral proteins are known, their relative importance on pathogenesis have not been thoroughly studied. In this regard, we aim to systematically map the mutational profile of different viral proteins to not only futher study their function but also their role in causing disease after infection.
Viral proteins encoded by SARS-CoV-2 contribute to disease development (Wong et al., Nat. Rev. Immunol., 2023).
Exberant and often persistent inflammatory responses have been observed in patients with severe disease after coronavirus infection. Such response is indispensable for virus clearance and establishment of protective immune response, however, when becomes dysregulated, causes severe disease. A fine balance between eliciting robust immune responses and preventing immunopathogenesis is required for protection against severe disease. We therefore aim to identify host factors and signaling pathways that are responsible for such exuberant responses. Examples include but not limited to eicosanoid signaling that impedes T cell activation (left) and dysregulated type I interferon signaling (right) that contribute to severe disease.
Robust and reliable models are essential in studying pathogenesis and evaluating vaccine and antiviral efficay. Since some animal species are naturally resistant to coronavirus infection, we developed severl methods to induce infection suscetibiliy in animals. These include introducing human receptor, either by viral vector through transgene expression and introducing compatible mutation to the virus by reverse genetics followed by mouse adaptation. We will leverage the advantages of different models for various purposes, such as investigating disease causing mechanism and identifying/evaluating vaccines and antivirals. We are also working to develop animal models for other human coronaviruses in which animal models have not been established.
Generation of a mouse-adapted SARS-CoV-2 as an animal model (Wong et al., Nature, 2023).