Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications

Muñoz-González, Sara; Ruggli, Nicolas; Rosell, Rosa; Pérez, Lester Josué; Frías-Leuporeau, Maria Teresa; Fraile, Lorenzo; Montoya, Maria; Cordoba, Lorena; Domingo, Mariano; Ehrensperger, Felix; Summerfield, Artur; Ganges, Llilianne

IL-10 is a well-characterised immunosuppressive cytokine that inhibits a broad spectrum of immune responses, including the suppression of stimulatory cytokine production, T-cell proliferation, and B-cell responses [64] [65] [66] [67] [68] . A previous study provided the ability of a highly virulent CSFV strain to induce detectable levels of IL-10 in the serum of pigs developing the acute form at 7 days post-infection [69] . However, IL-10 was not detected in any of the serum samples analysed from the persistently infected piglets. This finding could suggest that different roles are played by this cytokine in the two CSF forms. Nevertheless, the CSFV-and PHA-stimulated PBMCs from persistently infected piglets produced high levels of IL-10. In this regard, hepatitis C virus (HCV), which is also a member of the Flaviviridae family, induces the production of IL-10 by cells of the innate immune system, principally by monocytes. This response has been associated with the suppression of the adaptive immune response in HCV persistently infected patients [66, 70] . In this context, CSFV behaves in a similar manner to HCV, avoiding clearance by the immune system of the host. Moreover, the addition of neutralising IL-10 Ab did not restore the number of IFN-γ-producing cells in PBMCs from persistently infected piglets. Therefore, other mechanisms might also be involved in the general suppression of the T-cell response upon CSFV and mitogen activation. Previous studies have shown a drastic decrease in the T cell populations due to lymphocyte apoptosis during the acute form [59] , and it could be another factor preventing the activation of the adaptive immune response in persistently infected animals, which also showed PBMC depletion.