This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The antiviral role of RNA interference (RNAi) has been well established in plant and lower animal systems. The goal of this research is to determine if RNAi is an important defense against viruses infecting mammals. Most plant-infecting viruses encode suppressors of RNAi to ensure host invasion. We are systematically screening several animal virus genomes in collaboration with other NCV researchers for the presence of genes with RNAi suppressor activity. The viruses to be tested include a Rhabdovirus (VSV) in collaboration with the Pattnaik lab, a Flavivirus (Dengue) in collaboration with the Zhang lab, a member of the Arteriviridae (PRRSV) in collaboration with the Osorio lab and Human papillomavirus (HPV) in collaboration with the Angeletti lab. Two different approaches are being used to test the central hypothesis that RNAi is an integral part of the complex antiviral defense system in mammals. First, a plant based transient assay has been used to screen proteins from various mammal-infecting viruses for potential suppressors. These have included a systematic analysis a Rhabdovirus (VSV) in collaboration with the Pattnaik lab; a Flavivirus (Dengue) in collaboration with the Zhang lab; and a member of the Arteriviridae (PRRSV) in collaboration with the Osorio lab. Several candidate viral genes were identified with possible suppressor activity. Second, animal cell lines stably expressing p19, a suppressor with cross-kingdom silencing suppression activity, were generated and screened for enhanced susceptibility to several different mammalian cell infecting viruses including HIV in collaboration with the Wood lab.
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