Studies on Molecular Mechanisms of Host-Pathogen Interactions of Nidoviruses of Veterinary Importance

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The porcine reproductive and*respiratory syndrome virus (PRRSV) and the porcine epidemic diarrhea virus*(PEDV) are responsible for severe agricultural economic losses and are*considered to be the primary emerging livestock pathogens in Canada and worldwide.*Both viruses are single-stranded, positive-sense RNA, enveloped porcine*nidoviruses and share common characteristics including similar particle*structure, conserved genomic organization and replication strategy. The*traditional approach to develop vaccines has not resulted in reliable and*effective vaccines, and these viruses remain a major threat to the swine*industry worldwide.***We believe that insufficient*understanding of nidovirus-host interactions hinders the development of*effective vaccines against nidoviruses. Therefore, we propose to investigate the molecular mechanisms of animal*nidovirus-host interactions in order to identify novel antiviral targets and*develop effective prevention strategies.***The*long-term goal of this program is to gain a better understanding of the molecular*mechanisms of interactions between animal nidoviruses and their hosts in order*to develop new strategies for effective control of viral infections. The short-term*goal for the next five years is to elucidate PRRSV and PEDV interactions with*host cells by focusing on the characterization and comparison of early events*in nidovirus infection. To address this objective, we will: 1) investigate the*cellular and molecular mechanisms underlying porcine nidovirus entry into host*cells, and 2) analyze proteomic profiles of host cell responses to viral*infection, characterize the composition of nidoviruses, and identify the host*proteins associated with the viral particle. The accomplishment of these*specific objectives will lead to an understanding of the nature of the*virus-host interaction during the earliest stage of nidovirus infection. We*will identify cellular factors interacting with the viral genome and proteins,*as well as host proteins that are incorporated into viral particles and*involved in modulation of viral infection. We will map the highly conserved and*potent antigenic epitopes of viral proteins, which are transiently exposed*during the process of virus entry and represent important targets for vaccine*design. These results will provide tools and directions for the continuation of*our research program in the investigation of intracellular trafficking of the viral*genome and proteins within the host cell, the mechanisms of viral assembly and*release, and the cellular pathways exploited and rearranged by nidoviruses to*facilitate infection and evade host surveillance. More importantly, our*findings will provide new specific targets for antiviral vaccine development. Our*findings will also be relevant to many other enveloped animal viruses. *** ***