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CIHR-UBC Strategic Training Program for Translational Research in Infectious Diseases Address: D452 – 2733 Heather Pavilion, Vancouver, BC V5Z 3J5 E-mail: [email protected] Voice: (604) 875-5063 Fax: (604) 875-4013 Website: http://cmdr.ubc.ca/trainingprogram Research Theme: Pathogenomics, proteomics, vaccine development, diagnostics Sub-theme: Viral and cellular microarray-based studies of human hepatitis C virus and SARSassociated coronavirus Principal Investigator: Dr. François Jean, PhD; CIHR/Health Canada Scholar Telephone: Fax: E-mail: (604) 822-0256 (604) 822-6041 [email protected] Current antiviral therapeutic strategies are centered on a relatively small number of non-structural protein targets in the viral genome; for instance, there are less than ten such targets in HIV, influenza A, and hepatitis C viruses. Although initially successful, the usefulness of these strategies is limited: they are severely toxic and susceptible to circumvention by drug-resistant variants. An alternate strategy is to inhibit the function of host proteins that are essential for the virus to complete its replicative cycle. As obligate intracellular parasites, viruses critically depend on the biosynthetic components and cellular machinery for propagation and replication. During infection, viruses modulate host cell gene expression and influence cellular functions. A study of their impact on host gene expression will help us to learn about how they interact with their hosts. If the host proteins that are involved in the viral life-cycle could be inhibited without impairing the host, a broader array of targets for antiviral drug discovery would become available. This approach becomes viable if the virus-specific host-cell pathways can be determined. The recent successes achieved by using DNA-array technology to analyze virus-induced gene expression in host cells (processes termed ‘virogenomics’) suggest that this global systematic strategy could add substantially to both the approaches for identifying common- and/or virusspecific host-cell pathways essential for viral infection and the identification of new avenues for therapeutic intervention. It is our hypothesis that comparative virogenomics of multiple viral infections will identify virus-specific proteins and yield invaluable information about the host-cell intracellular pathways affected by important viral pathogens to either support viral replication or to counteract host-cell defense mechanisms. In this work, we are performing comparative virogenomics and viroproteomics to characterize a subset of complex viral infection programs and associated cellular regulatory networks through which hepatitis C virus (HCV), and SARSassociated coronavirus (SARS-CoV) cause human diseases. Updated: August 2003 Page 1