Single cell analysis reveals functional T cell deficits in transplant recipients with chronic Epstein-Barr Virus DNAemia compared to individuals with controlled infection 3846

Abstract Description Epstein-Barr Virus (EBV) infects 90-95% of adults globally. While typically self-limiting in immunocompetent individuals, uncontrolled viremia and life-threatening EBV+ post-transplant B cell lymphomas can occur in immunosuppressed individuals. A critical gap in the field is understanding the immune factors that distinguish transplant recipients who control EBV from those who develop EBV-related diseases. Therefore, we assessed T cell responses to latent cycle EBV peptides in PBMCs from transplant recipients that are controllers or who have chronic EBV DNAemia (CED), defined as elevated viral DNA loads for 3-6 months. Single cell gene expression and T cell receptor analysis showed significant downregulation of protein synthesis genes in CED, indicating reduced protein output and potentially reduced anti-EBV responses. Furthermore, analysis of EBNA3-specific T cells (defined by shared CDR3β motifs) highlighted distinct transcriptional profiles between cohorts, driven by the upregulation of negative T cell regulation genes and downregulation of migratory genes in CED. Thus, individuals with CED may have a defect in T cell activation and migratory capacity, that could facilitate viral evasion. Finally, PMA/ionomycin stimulation revealed reduced CD8+IL2+ memory T cells in CED, suggesting impaired function within the memory compartment. Together these findings unveil immune alterations that may contribute to the inability to control EBV infection in transplant recipients. Funding Sources Supported by NIH UO1 CA275305; NIH UO1 AI35957 (CTOTC-15); Stanford University’s Propel Program Topic Categories Viral Immunology (VIR)