An EBNA3A-mutated Epstein-Barr virus (EBV) retains the capacity for lymphomagenesis in a cord blood-humanized mouse model

EBV causes B-cell lymphomas and transforms B cells in vitro. The EBV protein, EBNA3A, collaborates with EBNA3C to repress p16 expression and is required for efficient transformation in vitro. We performed RNAseq to compare the phenotypes of an EBNA3A-mutated EBV, delta3A, versus wild-type, WT EBV, in a cord blood-humanized CBH mouse model. The hypomorph delta3A mutant in which a stop codon is inserted downstream of the first ATG, and the open reading frame disrupted by a 1 bp insertion, expresses very small amounts of EBNA3A using an alternative ATG at residue 15. Delta3A caused B-cell lymphomas at similar rates as WT EBV, but with delayed onset.