Exploration of the immune response to the Porcine Respiratory and Reproductive Syndrome Virus PRRSV by a modelling approach: conditions for viral clearance

International audiencePRRSV replicates mainly in the pulmonary macrophages which (i) are responsible for inflammation and viral destruction by phagocytosis and (ii) participate in the induction and orientation of the adaptive immune response. Experimental studies have shown that PRRSV is able to inhibit innate immunity, to reduce the gamma interferon synthesis and to limit the efficiency of neutralizing antibodies. Moreover the virulence and the resulting interaction with the host immune system are variable between viral strains. Our limited understanding of the interaction between the virus and the immune system is the main obstacle in the evaluation of control measures and the development of more efficient vaccines. To explore these complex mechanisms and test biological hypotheses, we propose an original model of the immune response centred on macrophage - virus interactions in the lung. Comparatively to previous modelling studies we highly detailed the temporal dynamics of the innate immune response to better understand the effect of the macrophage-virus interactions on the viral clearance. To explore the relative influence of the immune mechanisms on the infection outcome we conducted a multivariate sensitivity analysis using the R package multisensi. We showed that the first steps of macrophage-virus interactions are crucial. We used the model to explore the immune response to strains of variable virulence and to determine the required conditions for viral clearance