Stimulation of the porcine immune system causes increased replication of porcine circovirus 2 (PCV2) in vivo. In the present study, we investigated whether various
cytokines (
interleukin-1 [IL-1], IL-6, IL-10,
tumor necrosis factor-alpha [
TNF-alpha],
interferon-alpha [IFN-alpha], and IFN-gamma) are able to influence PCV2
infection in vitro. No changes were observed in
IL-1,
IL-6,
TNF-alpha, or IL-10-treated cells. However, it was demonstrated that IFN- alpha and IFN-gamma influenced PCV2
infection in porcine kidney cells (PK-15) and porcine monocytic cells (3D4/31). IFN-gamma added to the culture medium before, during, or after inoculation increased the number of PCV2
antigen- positive cells, respectively, by 418%, 171%, and 691% in PK-15 cells and by 706%, 114%, and 423% in 3D4/31 cells. IFN-alpha pretreatment decreased the number of infected PK-15 cells. When it was added after inoculation, IFN-alpha enhanced PCV2
infection by 529% in PK-15 cells and
by 308% in 3D4/31 cells. The effect of both IFNs on PCV2
infection was dose dependent and could be blocked with IFN-alpha or IFN-gamma
neutralizing antibodies. Leukocyte-derived porcine IFN-gamma induced a similar effect on PCV2
infection. Treatment of PK- 15 cultures with IFN-gamma caused a 20 times higher production of progeny virus. Confocal microscopy studies showed that the enhancing effect of IFN-gamma on PCV2
infection was achieved by increased internalization of PCV2 virionlike particles (VLPs). Binding of the VLPs to the cell or expression kinetics of PCV2
proteins in infected cells were not altered by IFN-gamma treatment. To our knowledge, this study reports the first enhancement of a
viral infection by treatment with type I or type II IFNs.