Location: Foreign Animal Disease Research2013 Annual Report
1a. Objectives (from AD-416):
The innate response of inflammatory cells in animals infected with foot-and-mouth disease virus (FMDV) has begun to reveal the immune evasion capabilities of this acute virus. Analysis of the natural killer cell (NK cell) response in FMDV infection has led to indications that the virus has evolved the capacity to induce short term, non-responsive state in these cells in swine. This project will now focus on the innate response in cattle. Should funds become available, we will continue analysis of swine responses as well. The objectives of this project are 1: To determine methods of activation of NK cells in response to FMDV infection. 2: To design soluble gamma-delta T cell receptor (sTCR) of bovine and to investigate the viral antigen binding capability of gamma-delta T cells . Antigens identified through the sTCR will be studied regarding their capacity to stimulate gamma-delta T cells.
1b. Approach (from AD-416):
1. Methods of activation of NK cells in response to FMDV infection will be determined through the analysis of the activation/suppression of NK cells. ARS, PIADC will provide Warsaw Univ. samples from infected bovine for analysis at PIADC. 2. Based on these data, Warsaw Univ. will design and assemble in vitro, soluble gamma-delta T cell receptors, screen the sTCR for antigen binding to delineate the nature of antigen type and assess the activation status of gamma-delta T cells with identified antigens. ARS, PIADC will screen the sTCR for FMDV antigen binding and examine the activation status of gamma-delta T cells following stimulation with FMDV.
3. Progress Report:
This goal of this research project is to understand the innate response of Foot-and-Mouth Disease Virus (FMDV) infection in cattle through the determination of methods to activate gamma delta T cells and (natural killer) NK cells against FMDV infected targets and to design a soluble gamma delta T cell receptor (sTCR) of bovine and to investigate the viral antigen binding capability of the gamma delta T cells. Antigens identified by the soluble TCR will be studied regarding their capacity to stimulate gamma delta T cells independently. Efforts were concentrated on testing viral double-stranded RNA (dsRNA) and its capability to stimulate bovine gammadelta T cells. Human and mouse studies have shown that dsRNA is able to activate specific population of gammadelta T cells to acquire secretory and cytolytic functions. Bovine gamma delta cells have properties of both innate and adaptive immune cells. However, detailed studies of how bovine gamma delta T cells execute their functions as innate or adaptive immune cells are lacking. In addition, their precise role in viral infections of cattle is not known. We have examined the reactivity of bovine gamma delta T cells to viral dsRNA isolated from bovine respiratory syncytial virus. Results suggest that viral dsRNA may induce expression of molecules that promote innate function of gamma delta T cells and are discussed in context of pathways for enhancing bovine gamma delta T cell function against viral infections. FY 2013 publications and abstracts include: 1. Toka FN, Golde WT, 2013. Cell mediated innate responses of cattle and swine are diverse during foot-and-mouth disease virus (FMDV) infection: A unique landscape of innate immunity. IMMUNOL. LETTERS 152 (2):135-143 2. Felix N. Toka E. Krukowska, W. T. Golde Reactivity of bovine WC1+ ¿d T cells to viral dsRNA. AAI Meeting in Honolulu, Hawaii, 3-7 May 2013. J Immunol 2013 190:141.16 3. Jared Patch, Pervaiz Dar, Ryan Waters, Felix Toka, and William Golde, Infection with foot-and-mouth disease virus induces a natural killer cell response in cattle. AAI Meeting in Honolulu, Hawaii, 3-7 May 2013. J Immunol 2013 190:141.7 4. Waters R., dar P., Patch J., Kenney M., Glabman R., Toka FN., Golde WT. Analysis of bovine natural killer (NK) cell and gammdelta T cell mediated cytotoxicity following infection with footy-and-mouth disease virus (FMDV). 4th European Veterinary Immunology Workshop (EVIW), Edinburgh, Scotland 2-4 Sept. 2012 No technologies were transferred during FY 2013.