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United States Department of Agriculture

Agricultural Research Service

Research Project: FOOT-AND-MOUTH DISEASE VIRUS (FMDV) HOST-PATHOGEN INTERACTIONS

Location: Foreign Animal Disease Research

Title: Natural killer cell dysfunction during acute infection with foot-and-mouth diseaase virus

Authors
item Toka, Felix
item Nfon, Charles - USDA ARS ORISE FELLOW
item Dawson, Harry
item Golde, William

Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 6, 2009
Publication Date: December 15, 2010
Citation: Toka, F.N., Nfon, C., Dawson, H.D., Golde, W.T. 2010. Natural killer cell dysfunction during acute infection with foot-and-mouth diseaase virus. Clinical and Vaccine Immunology. 16(12):1738-1749.

Interpretive Summary: The early, rapid and nonspecific response to virus infection can often control that infection without induction of adaptive immune responses. This is mediated by such things as induction of antiviral proteins like interferons that block virus proliferation within a cell. Also, there can be activation of cells with antiviral activities such as the natural killer cell (NK). These cells recognize virus infected cells via stress signals and kill these cells before new virus can be made. This blocks the spread of virus through the body and to other individuals. Here, we analyzed the role of NK cells in foot-and-mouth disease virus infection in pigs. We show that during the acute infection, the ability of NK cells to function is lost, thereby allowing the virus to spread. This “immune evasion” capacity of FMDV is another aspect of this virus that makes it such a contagious pathogen.

Technical Abstract: 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 with FMDV and tested ex vivo and show that NK-dependent cytotoxic activity against a tumor cell 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 resulted in the alteration of mRNA expression from critical receptor genes in porcine NK cells including SH2D1B, NKG2A (inhibitory) and NKp80, NKG2D (activating). These data indicate that this virus infection negatively influences the capacity of NK cells to recognize and eliminate FMDV infected cells. In addition, reduction in NK cell cytotoxicity coincided with the increase in virus titers, consistent with the virus blocking NK cell associated innate responses. This effect likely plays a role in immune evasion, allowing the virus to replicate and disseminate within the host.

Last Modified: 4/19/2014
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