PRRSv infection has been shown to cause an acute lymphopenia (loss of cells in the blood), lymphadenopathy (increased size of lymph nodes due to increased cell numbers) and thymic atrophy (decreased thymus size due to decreased number of cells) in conjunction with PRRSv antigen staining in the thymus; however, the relationship between these features and subsequent immune dysregulation has not been evaluated. Lymphopenia coincidental with impaired thymic output is likely to have a significant impact on the peripheral pool of functional T cells. Ultimately, this would impair the ability of the pig to mount a protective immune response and clear the virus, a characteristic feature of PRRSv pathogenesis. Work from this proposal shows that the thymus is significantly impacted by PRRSV infection, but severity is impacted by the challenge strain. Infection with the moderately pathogenic strain (SDSU73) did have an impact on thymic cellularity and changes in gene expression, but these changes were limited within the first few weeks post-infection, with near resolution to normal by day 21 following challenge. In stark contrast, the effect on the thymus is more pronounced following infection with JXwn06 highly-pathogenic PRRSV and there is no indication of resolution to normal. Interestingly, there are a large number of dying cells in the thymus following challenge, but these areas are not the same as where the virus is located. This indicates that the loss in cells may be an indirect effect of infection. Overall, the changes in gene transcription will provide useful data for further characterizing how cells are changing following infection, and ideally lead to identifying interventions to lesson the negative impact of infection on this important lymphoid organ.