EBV INFECTION OUTCOMES DETERMINED BY MONOCYTE AND TREG-DRIVEN IMMUNE DYNAMICS IN AN EX VIVO PBMC MODEL [RNA-Seq EBV enrich]

Inhibitors of LIPA increased EBV titers during primary infection, indicating that LIPA is part of an early monocyte-driven antiviral response. At later timepoints post-infection, donor-dependent variability in lymphoblastoid cell line (LCL) outgrowth was associated with divergent immune states. Donors that failed to generate LCLs demonstrated increased frequencies of CD8+ T cells and reduced numbers of regulatory T cells (CD4⁺CD25⁺FOXP3⁺).

EBV transcriptomics revealed that LCL-failed donors exhibited elevated early lytic gene expression but did not establish a type III latency program. Our findings suggest that individual variations in immune cell composition and gene expression may account for differences in the immune response to EBV. These findings define temporal immune and viral signatures that predict transformation outcome and highlight intact PBMCs as a tractable model to study EBV pathogenesis in a genetically diverse, human-specific context.