EBNA2-deleted Epstein-Barr virus (EBV) strain, P3HR1, causes Hodgkin-like lymphomas and diffuse large B cell lymphomas with restricted latency types in humanized mice

Here we show that a naturally occurring EBNA2-deleted EBV strain (P3HR1) isolated from a human BL induces EBV-positive B-cell lymphomas in a subset of infected cord blood-humanized (CBH) mice. Furthermore, we find that P3HR1-infected lymphoma cells support two different viral latency types and phenotypes that are mutually exclusive: 1) Large (often multinucleated), CD30-pos cells reminiscent of the Reed-Sternberg (RS) cells in CHL that express high levels of LMP1 but not EBNA-LP (consistent with type II viral latency); and 2) smaller monomorphic CD30-neg DLBCL-like cells that express EBNA-LP and EBNA3A but no LMP1 (consistent with Wp-restricted latency). These results reveal that EBNA2 is not absolutely required for the ability of EBV to form tumors in CBH mice and suggest that P3HR1 virus can be used to model EBV positive lymphomas with both Wp-restricted and type II latency in vivo.