Paper Title
Porcine Reproductive and Respiratory Virus (PRRSV) Alters Thymocyte Development and Repertoire of T Lymphocytes

Abstract
PRRSV is a major threat to global pork production because it is a pandemic and previous research has not clarified the pathology that allows the virus to persist in young pigs. Our recent research has shown that PRRSV infects the thymus and alters the T-cell receptor repertoire during T lymphocyte development. Developing thymocytes are affected during negative selection when they transit from the triple-negative to the double-positive stage just before entering the medulla at the corticomedullary junction. As a result, PRRSV-specific T cells are selectively eliminated so that they are absent from the periphery. The "hole" in the T-cell repertoire allows acceptance of PRRSV epitopes as self-antigens, resulting in the absence of a specific immune response against PRRSV. Without adequate and sufficient PRRSV-specific T cells, selection of B cells capable of producing neutralizing antibodies with high affinity is impaired, as is the generation of specific cytotoxic T cells. Interestingly, PRRSV does not act as a superantigen but affects the T-cell repertoire specifically for each animal, suggesting aberrant selection of T-cell receptors by MHC-I and MHC-II. The lack of an effective immune response against the critical viral structures tolerated as self-antigens, but the chronic stimulation of the immune system by the presence of innate viral structures and byproducts, allows the virus to escape, survive, persist, and spread throughout herds. This strategy of PRRSV may elucidate a reason for the immune system dysregulation observed during infection, which has not yet been satisfactorily explained. This work was supported by grant 20-03282S from the Czech Science Foundation and authors declare no competing financial interests. Keywords - Veterinary Immunology, Thymus, Lymphocyte Development, Adaptive Immunity.