Specific Goals
To determine the mechanism of PLA2G2D upregulation and the role of PLA2G2D in vaccine responses in 12m old mice. To determine the role of PGD2-DP1 signaling in the immune response to SARS-CoV in 12 m mice. To determine whether PGD2 and PLA2G2D contribute to poorer outcomes in mice infected with MERS-CoV, another infection in which severity is age-dependent.
Identify adaptive mutations responsible for MERS-CoV pathogenesis in mice. Determine how MA mutations affect spike structure and function. Identify the proteases activating MERS-CoV in vivo. Identify host cell factors controlling MERS spike protein evolution.
To understand how an in vivo evolved MERS-CoV causes lethal lung disease. To investigate how DPP4 abundance and function influence MERS disease pathogenesis.
To identify virus: host interactions that induce lung edema. To develop safe live-attenuated vaccines for MERS-CoV.