CVI Accepts, published online ahead of print on 14 October 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00280-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Natural killer cell dysfunction during acute infection with foot-and-mouth disease virus (FMDV)

Felix N. Toka, Charles Nfon, Harry Dawson, and William T. Golde^*

Plum Island Animal Disease Center, Agricultural Research Service, USDA, Greenport NY, 11944; Department of Preclinical Science, Faculty of Veterinary Medicine, Warsaw University of Life Science, Warsaw, Poland; Beltsville Area Research Center, ARS, USDA, Beltsville, MD 20705

^* To whom correspondence should be addressed. Email: william.golde{at}ars.usda.gov.

Natural killer cells (NK) provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. The role of these cells in foot-and-mouth disease virus (FMDV) infection is unknown. Previously, we characterized the phenotype and function of NK cells from swine. In the present study, we report the analysis of NK cells isolated from animals infected with FMDV and tested ex vivo and show that NK-dependent cytotoxic activity against tumor cells as targets was impaired. More relevant to this infection, killing of target cells infected with FMDV was also inhibited. Further, the proportion of NK cells capable of producing IFN and storing perforin was reduced. PBMC isolated from infected animals are not productively infected but virus exposure in vivo resulted in significant induction of NKp30 and TLR 3 expression and moderate activation of SOCS3 and IL15 receptor mRNA. However, there was little alteration of mRNA expression from a number of other receptor genes in these cells including SH2D1B, NKG2A (inhibitory) and NKp80, NKp46 and NKG2D (activating). These data indicate that this virus infection may influence NK cells ability to recognize and eliminate FMDV infected cells. In addition, reduction in NK cell cytotoxicity coincided with the increase in virus titers, indicating virus blocking of NK cell associated innate responses, albeit temporarily. These effects likely culminate in brief but effective viral immune evasion, allowing the virus to replicate and disseminate within the host.