Turkey arthritis reovirus: pathogenesis and immune response

In 2011, turkey reoviruses were isolated from tendons and synovial fluids of >15-week-old lame turkeys displaying swollen joints and occasionally ruptured leg tendons in Midwest, USA. These reoviruses were tentatively called turkey arthritis reoviruses (TARV) to differentiate them from reoviruses isolated from intestinal contents and feces of turkeys namely turkey enteric reoviruses (TERV). TARV were found to be genetically distinct from chicken arthritis reoviruses (CARV). Five experiments were conducted to test the pathogenicity of TARV in turkeys and in chickens and to compare it with that of TERV and CARV. Additionally, this work investigated the virus pathogenesis and cytokine immune responses. TARV showed unique capability to induce significantly higher tenosynovitis scores in turkeys as compared with TERV and CARV which induced minimal scores. Clinical lameness was first displayed at 8 weeks of age in TARV-inoculated turkeys at 1 week of age. Lameness in infected group reached approximately 50% at 16 weeks of age. TARV did not induce any lesions in chickens via intratracheal or oral route. TARV inoculation via footpad route induced tenosynovitis in chickens at 2 and 3 weeks PI with no clinical lameness. In pathogenesis study, TARV displayed the greatest replication in intestines and bursa of Fabricius than in leg tendons of turkeys. Viral infection mediated effective antiviral cytokines immune response that limited virus replication in the intestines. Furthermore, viral infection mediated a significantly elevated T helper-1(Th1) cytokine response in intestines and tendons and minimal Th2 and Th17 cytokine response during the early stage (2 weeks) of infection. This work established an experimental model to study TARV which provides early end points that are indicative of disease pathogenicity. Additionally this work developed a new grading system for histologic tenosynovitis which can be used in a wide variety of experimental models. For lameness evaluation in turkeys, this work developed a grading system for gait scores. In summary, this work showed unique pathogenicity of the newly isolated TARV and added significant knowledge to TARV pathogenesis and immune response using the newly established reproducible experimental model and the newly developed grading systems for evaluation of tenosynovitis and clinical lameness.