Grant: Project Grant

Enterovirus infections are associated with several acute and chronic diseases worldwide and in Canada. Most enterovirus infections are cleared by the immune system, however, infection by certain enteroviral species and strains can be more severe. Poliovirus is the most well-known member which causes paralytic poliomyelitis. The non-poliovirus members are more common such as rhinovirus, which causes the common cold, and coxsackievirus and EV71, which are associated with more debilitating diseases such as viral myocarditis, Type I diabetes, and hand-foot-and-mouth disease, and in rare cases, meningitits. Although enteroviruses have been studied for several decades, the molecular basis of infection and the pathogenic mechanisms leading to disease are still poorly understood. One of the signature properties of enteroviruses is that the virus expresses a protein, called a protease, which cleaves host proteins in the cell to facilitate virus infection. Currently, the extent of host proteins targeted by the viral protease is not known. In this study, we will utilize a novel unbiased proteomics approach to comprehensively identify all of the targets of the proteases from coxsackievirus. Unlike other methods, this new approach is sensitive and can identify the location of the cleavage site on the target protein. The identification of novel targets will provide a catalog of the host processes that viruses affect. Importantly, the knowledge gained will allow us to identify new targets for antiviral therapy. The development of this strategy can be exploited to identify the repertoire of host targets of proteases from other viruses.