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Title: Suppression of Swine NK Cell Function During Acute Infection with Foot-and-Mouth Disease Virus (FMDV)

Author
item Toka, Felix
item NFON, CHARLES - ORISE, ARS-PIADC FELLOW
item Golde, William

Submitted to: European Study Group on the Molecular Biology of Picornaviruses
Publication Type: Abstract Only
Publication Acceptance Date: 3/21/2008
Publication Date: 5/26/2008
Citation: Toka, F., Nfon, C.K., Golde, W.T. 2008. Suppression of Swine NK Cell Function During Acute Infection with Foot-and-Mouth Disease Virus (FMDV). European Study Group on the Molecular Biology of Picornaviruses. P 94

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals and causes an economically devastating disease. This highly acute infection has multiple negative effects on the innate response, presumably contributing to the rapid spread of virus within the host. Understanding the regulation of innate responses during infection may lead to a more rational design of vaccines against FMDV. We examined the reactivity of swine NK cells after infection of Yorkshire pigs with FMDV strain 01 Campos. NK cells were tested for their capability to kill a tumor line target in vitro, a cell line infected with FMDV, for the expression of intracellular perforin and the secretion of IFN'gamma. Baseline NK cell cytotoxicity from non-infected pigs ranged from 5 to 10% and was marginal against FMDV-infected SK6 cells compared to uninfected cells. However, NK cells could be stimulated to efficient lysis of FMDV infected cells when stimulated with cytokines (IL15 or IL12 plus IL18), also compared to uninfected SK-6. In vivo, infection with O1 Campos resulted in reduced NK cell lytic activity against tumor cell targets compared to baseline cytotoxicity. NK cells also lose the ability to lyse FMDV-infected SK6 cells ex-vivo and IFN'gamma'secretion by NK cells during the acute infection did not increase. Perforin expression increased but did not correlate with the killing capability of the NK cells. Increase in serum levels of IL-12, IL-15 and IL-18 was not observed as opposed to serum samples originating from animals infected with an attenuated strain of FMDV in which these cytokines increased from day 2 post infection. The decline from baseline cytotoxicity in infected pigs coincided with the onset of lymphopenia. These results indicate a suppression of innate NK cell responses by FMDV. Manipulating the innate responses to overcome viral evasion may enhance rapid acting vaccines for foot-and-mouth disease.