Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses

The polarization into M1 and M2 macrophages (M Phi)) is essential to understand M Phi function. Consequently, the aim of this study was to determine the impact of IFN-gamma (M1), IL-4 (M2) and IFN-beta activation of M Phi on the susceptibility to genotype 1 and 2 porcine reproductive respiratory syndrome (PRRS) virus (PRRSV) strains varying in virulence. To this end, monocyte-derived M Phi were generated by culture during 72 h and polarization was induced for another 24 h by addition of IFN-gamma, IL-4 or IFN-beta. M Phi were infected with a collection of PRRSV isolates belonging to genotype 1 and genotype 2. Undifferentiated and M2 M Phi were highly susceptible to all PRRSV isolates. In contrast, M1 and IFN-beta activated M Phi were resistant to low pathogenic genotype 1 PRRSV but not or only partially to genotype 2 PRRSV strains. Interestingly, highly virulent PRRSV isolates of both genotypes showed particularly high levels of infection compared with the prototype viruses in both M1 and IFN-beta-treated M Phi (P < 0.05). This was seen at the level of nucleocapsid expression, viral titres and virus-induced cell death. In conclusion, by using IFN-gamma and IFN-beta stimulated M Phi it is possible to discriminate between PRRSV varying in genotype and virulence. Genotype 2 PRRSV strains are more efficient at escaping the intrinsic antiviral effects induced by type I and II IFNs. Our in vitro model will help to identify viral genetic elements responsible for virulence, an information important not only to understand PRRS pathogenesis but also for a rational vaccine design. Our results also suggest that monocyte-derived M Phi. can be used as a PRRSV infection model instead of alveolar M Phi, avoiding the killing of pigs. (C) 2013 Elsevier B.V. All rights reserved.