The use of new in vitro models to study the pathogeneis of the most important diseases of the respiratory tract of swine

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The two most important animal diseases in term of economical loss in swine industry worldwide are porcine reproductive and respiratory syndrome (PRRS) and postweaning multisystemic wasting syndrome (PMWS). The etiological agents involved in those two major swine diseases are PRRS virus (PRRSV) and porcine circovirus (PCV) type 2 (PCV2), respectively. PRRSV and PCV2 are airborne transmitted. Airborne transmitted pathogens need to interact with host cells of the respiratory tract such as porcine epithelial cells and porcine alveolar macrophages (PAM) in order to be able to enter and disseminate in the host organism. PCV2 and PRRSV are known to have a restricted cell tropism in vivo and in vitro. The replication of PCV2 in PAM is usually very poor but there is a high amount of PCV2 in the lungs of sick animals. Consequently, the epithelial cells of the respiratory tract of swine may play an unexpected role in the viral pathogenesis compared to PAM, which are extensively studied. Until now, no experiment involving the study of the interaction of these viruses with epithelial cells of the respiratory tract of swine has been conducted. Interestingly, two new immortalized cell lines of the respiratory tract of swine, the NPTr and SJPL cells, have been discovered to be permissive to PCV2 and PRRSV infection and replication in vitro, respectively. Thus, the main goal of the present research proposal program is to use these new immortalized cell lines to study the viral pathogenesis of PRRSV and PCV for the acquisition of new knowledge and the improvement of the animal health . The specific objectives are: 1) to use the new PCV/NPTr infection model to study the viral pathogenesis, the immune response modulation and use the reverse genetic experimental approach to establish the existence of virulence variations between PCV types and genotypes; 2) to study the synergy and immune modulation of PRRSV in NPTr cells infected by PCV; 3) to determine if a PRRSV vaccine produced with the SJPL cells could improve the immune response and protection in vaccinated and challenged pigs.