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Title: Interferon Alpha Production by Circulating 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 Golde, William

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

Interpretive Summary: Viral infections are often characterized by interference of the host immune response to the infection. This “immune evasion” serves to create a favorable environment for the virus. Here we describe analysis of blood cells critical to both early and long term immunity during infection of pigs with foot-and-mouth disease virus (FMDV). These studies show that the virus is able to block the early, anti-viral functions of these blood cells, and there is no effect on functions related to lasting immunity to the virus. This process allows the virus to multiply and spread to other members of the herd and in part explains the highly contagious nature of FMDV.

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 the innate response to the virus. In vivo, FMDV induces lymphopenia and reduced T cell proliferative responses to mitogen, viral effects that may contribute to evasion of early immune responses. In this study we analyzed the in vivo effects of FMDV infection on the innate response of two populations of dendritic cells. During the acute phase of infection of swine, production of IFNa from monocyte-derived DCs (MoDCs) and skin-derived DCs (skin DCs) is inhibited. This effect is 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. The inhibition of the innate response of dendritic cell populations in the blood and skin may enhance viral pathogenesis in infected animals.