Pathologic thymic atrophy caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection is time- and pathogenicity-dependent 2242731

Abstract Introduction Pathologic thymic atrophy disrupts immune developmental processes in the thymus and can have short- and long-term negative impacts on immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) causes thymic atrophy in pigs, yet progression of PRRSV-induced thymic atrophy and dependency on pathogenicity of infecting PRRSVs has not been well defined. Methods Time- and pathogenicity-dependent features of PRRSV-induced thymic atrophy were established by analyzing thymi collected from pigs infected with variable pathogenicity PRRSVs at 2, 6, and 10 days post-infection. Collected tissues were analyzed via whole genome sequencing and microscopic assessments. Results Microscopically, PRRSV detection, corticomedullary blurring, cell depletion, and apoptosis became more severe as post-infection time progressed and was exacerbated by more pathogenic PRRSVs. Gene expression changes detected via whole transcriptome sequencing increased with post-infection time and were exacerbated by more pathogenic PRRSVs. Gene set enrichment analysis for cell type-specific gene signatures suggested gene changes occurred due to thymocyte depletion, which was supported by microscopic assessment. Conclusion Results demonstrate synergistic dynamics of post-infection time and PRRSV pathogenicity in causing more severe thymic atrophy through microscopic and transcriptional alterations. Future work may address what the short- and long-term immune repercussions of PRRSV-induced thymic atrophy are and what specific viral attributes contribute to more severe thymic atrophy caused by highly pathogenic PRRSVs. Funding Source USDA ARS project #5030-32000-230-000-D Topic Categories Veterinary and Comparative Immunology (VET)