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Main objective:The main goal of this research is to study the impact of PRRSV/PCV co infections in a new cellular model,the NPTr-CD 163 cells.Specific objectives:-Test NPTr-CD163 cells for permissivity to PCV (PCV2a,PCV2b,PCV1 and PCV1/2a) and PRRSV (IAF-Klop).-Measure kinetic of replication of each viruses in co-infected cells.-Test if the modulation in kinetic of replication observed in PRRSV and PCV is induce by cell mortality or apoptosis.-Test if the modulation in kinetic of replication observed in each virus is dependent on cytokines production.Brief methods:Porcine newborn pulmonary tracheal cells (NPTr cells) were known to be only permissive to PCV2 virus,and not to PRRSV.Thus,NPTr cells were genetically modified with CD163 gene,a major PRRSVs cell receptor,to obtain PRRSV permissivity.Thus,those cells were tested for permissivity with PRRSV and other PCV genotypes (PCV2a,PCV2b,PCV1 and PCV1/2a).Then,kinetic replication of each virus in co-infected cells was performed during a 72 hour time course and viral production was measure using the K(a)rber method.Cell mortality of co-infected cells was measured using lactate dehydro,genase (LDH) release and apoptosis was quantified using caspase 3-enzyme activity.Cytokines mRNA was quantified with qRT-PCR.Summary of the results:NPTr-CD163 cells were found to allow complete viral replication of PRRSV and all tested PCV genotypes.Kinetic replication of each virus in co-infected cells show modulation of both virus replications depending on PCV genotype,as PCV 1 replication is down regulated and PCV2b replication is up regulated in co-infection with PRRSV compared to PCV infection alone.Inversely,PCV1 increases PRRSV replication,whereas PCV1/2a,PCV2a and PCV2b significantly lower PRRSV replication.Also,cell mortality is increase in co-infected cells compared to both single infected cells.Moreover,caspase 3-enzyme activity is increase in PCV2a/PRRSV co-infected cells compared to cells infected with each single infection.RT-qPCR cytokines mRNA expression analyses showed that TNF-αt and IFNβ were significantly increased in the PCV1-PRRSV co-infection model compared to single infections,whereas they remained low for the other PCV genotvpes.