High IFN-alpha responses associated with depletion of lymphocytes and natural IFN-producing cells during classical swine fever.

During the acute phase of the viral hemorrhagic disease, classical swine fever (CSF), a severe hematologic depletion in primary lymphoid organs and depletion of peripheral blood T and B lymphocytes are observed. The onset of these pathologic events is before viremia and independent of leukocyte infection, indicating a host-mediated effect possibly through a cytokine storm. Here, we show that high serum levels of interferon- α (IFN-α) were found during this phase of CSF, detectable as early as 2 days postinfection and reaching maximum levels 3–5 days postinfection (250–1300 U/mL). This IFN-α response was related to the virulence of the viral strain used, with avirulent virus not inducing any detectable serum IFN-α. A progressive depletion of natural IFN-producing cells/plasmacytoid dendritic cells (pDC), the likely in vivo source of IFN-α, was also induced by the viral infection. An important finding was that the onset of severe lymphopenia was concomitant with the IFN-α responses, and all animals with ser...