Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses.
The polarization into M1 and M2 macrophages (MΦ) is essential to understand MΦ function. Consequently, the aim of this study was to determine the impact of IFN-γ (M1), IL-4 (M2) and IFN-β activation of MΦ on the susceptibility to genotype 1 and 2 porcine reproductive respiratory syndrome (PRRS) virus (PRRSV) strains varying in virulence. To this end, monocyte-derived MΦ were generated by culture during 72h and polarization was induced for another 24h by addition of IFN-γ, IL-4 or IFN-β. MΦ were infected with a collection of PRRSV isolates belonging to genotype 1 and genotype 2. Undifferentiated and M2 MΦ were highly susceptible to all PRRSV isolates. In contrast, M1 and IFN-β activated MΦ 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-β-treated MΦ (P<0.05). This was seen at the level of nucleocapsid expression, viral titres and virus-induced cell death. In conclusion, by using IFN-γ and IFN-β stimulated MΦ 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 MΦ can be used as a PRRSV infection model instead of alveolar MΦ, avoiding the killing of pigs.
Faculty of Veterinary Medicine, University of Murcia, "Mare Nostrum Excellence Campus - 37 38", Murcia, Spain.
Obdulio
O
García-Nicolás
Institute of Virology and Immunology, Mittelhäusern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
Arnaud
A
Baumann
Institute of Virology and Immunology, Mittelhäusern, Switzerland.
Nathalie Jane
NJ
Vielle
Faculty of Veterinary Medicine, University of Córdoba, Campus Universitario de Rabanales, 'International Excellence Agrifood Campus, CeiA3', 14071 Córdoba, Spain.
Jaime
J
Gómez-Laguna
Faculty of Veterinary Medicine, University of Murcia, "Mare Nostrum Excellence Campus - 37 38", Murcia, Spain.
Juan José
JJ
Quereda
Faculty of Veterinary Medicine, University of Murcia, "Mare Nostrum Excellence Campus - 37 38", Murcia, Spain.
Francisco José
FJ
Pallarés
Faculty of Veterinary Medicine, University of Murcia, "Mare Nostrum Excellence Campus - 37 38", Murcia, Spain.
Guillermo
G
Ramis
Faculty of Veterinary Medicine, University of Córdoba, Campus Universitario de Rabanales, 'International Excellence Agrifood Campus, CeiA3', 14071 Córdoba, Spain.
Librado
L
Carrasco
Institute of Virology and Immunology, Mittelhäusern, Switzerland. Electronic address: artur.summerfield@ivi.admin.ch.
Artur
A
Summerfield
D000818:Animals; D002478:Cells, Cultured; D005838:Genotype; D007372:Interferons / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D013552:Swine; D014774:Virulence
D015847:Interleukin-4; D007372:Interferons
Genotype; Interferon; Macrophage; Polarization; Porcine reproductive and respiratory syndrome