Program Project
The human coronavirus-SARS (SARS-CoV) is the sole agent of Severe Acute Respiratory Syndrome (SARS). Given the significant morbidity and mortality caused by SARS-CoV infections, it is important that we understand the pathogenesis of this infection, in order to design effective vaccines and anti-viral therapy. Coronaviruses, particularly murine coronaviruses, have been extensively studied in the past 20 years. The investigators involved with this project have extensive experience in the pathogenesis and molecular biology of, and host immune response to, coronaviruses and other infections. The central objective is to characterize the interaction of SARS-CoV with the immune system and with target cells in the respiratory tract.
- To develop a murine model of SARS-CoV using recombinant SARS-CoV and HCoV-OC43, a coronavirus that causes the common cold. To examine SARS-CoV proteins for their ability to modulate the immune response in the context of coronavirus infections.
- To determine if SARS-CoV proteins modulate the adaptive immune response, dendritic cell function or lung pathology, using well characterized infectious models of respiratory viral infections. To begin to identify CD8 T cell epitopes recognized in humans infected with SARS-CoV using HLA-A-2 transgenic mice.
- To study interactions of SARS-CoV with airway epithelia using well differentiated cultures of human airway epithelia. To investigate the role of siRNA in modifying the airway cell infection caused by SARS-CoV.
- To study interactions of the surface glycoprotein, responsible for binding to susceptible cells, with its host cell receptor, with particular reference to human airway cells. To identify domains of the SARS-CoV S protein that are critical in pathogenesis.
