Objective:
Previous collaborative work between USDA, ARS, PIADC and the University have resulted in the development of tools to study the action of natural killer (NK) cells in cattle and swine. NK cells are of interest as they have the potential to eliminate virus early in infection and, because they are not specific to viral antigen, NK mediated protection would be pan FMDV serotype. The objective of this collaborative agreement is to develop a standard biological assay for the assessment of NK activity in infected and vaccinated animals.

Approach:
Rapid acting antiviral agents function via the innate response of cells creating an antiviral state. In our research program to improve the capacity to develop tools for rapid response to an outbreak of foot-and-mouth disease (FMD), induction of innate responses has been a central topic. Although a great deal has been learned about the action of various cytokines in the induction of the antiviral state on a cellular level, i.e. making cells refractory to infection, little is known about cellular innate responses. Early in infection, the principal cells mediating killing of virus infected cells are the natural killer (NK) cells. Data analyzing these cells from human blood, nonhuman primates and now swine, indicate that there are specific cytokines involved in activation of innate responses mediated by NK cells. Activation of NK cells can be easily assayed by increased killing activity on appropriate target cells. Importantly, this increased killing activity correlates with increased expression of two cell surface proteins on NK cells, CD16 and CD244. UTMB scientists have recently isolated monoclonal antibodies to the bovine homologues of the proteins and these can be used to assess activation status of bovine NK cells. Concurrently, investigators at USDA-ARS, Plum Island have shown that NK cells of swine recognize and kill FMDV infected cells. This agreement is designed to combine knowledge and efforts to accelerate the research activities of these collaborators. Using coordinated approaches, this Agreement seeks to understand the biology of activation of NK cells in cattle and swine and develop tools and protocols with the potential to be used as countermeasures in the face of an FMDV outbreak.