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Title: Interferon Alpha Production by Swine Dendritic Cells is Inhibited During Acute Infection with Foot-and-Mouth Disease Virus (FMDV)

Author
item NFON, CHARLES - ORISE, USDA, ARS, PIADC
item Ferman Ii, Geoffrey
item Toka, Felix
item Gregg, Douglas
item Golde, William

Submitted to: Viral Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2007
Publication Date: 3/20/2008
Citation: Nfon, C.K., Ferman Ii, G.S., Toka, F.N., Gregg, D.A., Golde, W.T. 2008. Interferon Alpha Production by Swine Dendritic Cells is Inhibited During Acute Infection with Foot-and-Mouth Disease Virus (FMDV). Viral Immunology. 21(1):68-77. doi: 10.1089/vim.2007-0097.

Interpretive Summary: The resistance to viral infections in most mammals involves cells that mediate an “innate” response. These cells use receptors that are somewhat nonspecific to sense the presence of microbes that may cause disease. One of the most critical types of cell carrying on this function is the dendritic cells. In this paper, we analyze two types of dendritic cells, one from the blood and another from the skin. In uninfected animals, these cells respond to stimulation by making the anti-viral protein, interferon. Remarkably, we now show that both of these dendritic cells, when isolated from animals infected with foot-and-mouth disease virus, have lost the capacity to make interferon. This is the observation even though these cells are not infected with the virus. We propose that virus infected cells make molecules of either cellular or viral origin, that inhibit this important dendritc cell function.

Technical Abstract: Viruses have evolved multiple mechanisms to evade the innate immune response, particularly the actions of interferons (IFN). We have previously reported that exposure of dendritic cells (DCs) to foot-and-mouth disease virus (FMDV) in vitro yields no infection and induces a strong IFN response indicating DCs may play a critical role in innate response to the virus. However, FMDV infection is characterized by rapid replication and spread within an individual and between animals. In addition, FMDV induces lymphopenia and reduced T cell proliferative responses to mitogen. In this study we analyzed the in vivo effects of FMDV infection on the innate response of DCs. During the acute phase of infection of swine, production of IFN alpha from monoycte-derived DCs (MoDCs) and skin-derived DCs (skin DCs) is inhibited, concurrent with rising viral titer in the blood. However, these cells are not productively infected. Interestingly, there are no changes in the capability of these DCs to uptake particles and process antigens indicating that the antigen presenting cell function is normal. Therefore, the inhibition of innate cytokine production of skin DCs and MoDCs during peak infection may enhance viral pathogenesis by permitting rapid replication and spread of the virus to other hosts before viremia can be cleared.