Effect of co-infections on the pathogenesis of the most important swine viruses

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Swine viruses are being investigated but predominantly in a context of single infections. Unfortunately, this type of investigation do not represent real life situation. In reality, several pathogens commingle together in a single animal reducing dramatically the efficiency of pathogens-specific treatments and making it more difficult to implement prophylactic measures. Therefore, the investigation of co-infections is a logical step to understand the outcome and how to treat infectious diseases. Associations of multiple infectious agents in the respiratory tract constitute what is known to be the porcine respiratory diseases complex. Several pathogens are included in that complex such as porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV), and swine influenza virus (SI), which are the etiological agents involved in postweaning multisystemic wasting syndrome (PMWS), PRRS, and swine flu infectious diseases, respectively. In addition, deoxynivalenol (DON) mycotoxin, a mold product, is a major contaminant of cereal grains and pigs are exposed chronically to DON because of their diet. Pig immune system is particularly sensitive to DON. The most important animal disease, in term of economical loss in swine industry worldwide, is PRRS (150 million $/year in Canada). During the 2005 PMWS outbreak, 200,000 pigs/years died in Quebec herds. Another major disease is swine flu. It is highly prevalent in swine herds and it causes a mortality of around 2.5% in swine productions. Thus, the main goal of the present research program is to further characterize the mechanisms involved in the pathogenesis of co-infections in swine and to better understand at a cellular level why there is in some instance an antagonism (which could lead us to the discovery of new antiviral drugs) and in other instance a synergy between swine pathogens during co-infections. To help us investigate swine co-infections, new virus permissive cell lines were recently genetically modified to render them permissive to more than one swine virus. Thus, the main objective of the present five years research program is to investigate the pathogenesis of PRRSV, PCV2 and SI co-infections in various combinations and DON/PRRSV co-infection, to better understand the host responses that could be involved in virus promotion and/or inhibition. Several parameters will be studied during co-infection experiments such as: virus replication kinetics, cell cycle/cell death (fluorescent microscopy, enzymatic assays, etc.), cytokines (qPCR, ELISA), and cellular pathways modulation (RNAseq, CRISPR/Cas9). In conclusion, the study of swine co-infections will give us a better understanding of the swine viral pathogenesis in a more realistic field condition and subsequently will lead to new discoveries with high applied potential for the control and treatment of swine viral infectious diseases.