Epstein-Barr virus induces host shutoff extensively via BGLF5-independent mechanisms [RNA-seq]

This study characterizes the effects of Epstein-Barr virus (EBV) reactivation on the host and virus transcriptomes. For this work, a dual-fluorescent lytic reporter (DFLR) EBV was constructed based on the M81 EBV strain and used to transform primary B cells into lymphoblastoid cell lines (LCL). Deposited here is RNA-seq data from these DFLR LCLs that were induced by BCR crosslinking and sorted into latent, early lytic, and late lytic fractions. All samples consist of 40,000 sorted cells and include equal quantities of ERCC spike-in RNAs for normalization. We also performed the same experimental approach on a second DFLR LCL in which the EBV BGLF5 host shutoff nuclease was deleted. This allowed us to define which changes in the transcriptome during EBV replication were due to BGLF5. This approach demonstrated extensive shutoff of host genes during EBV replication and, unexpectedly, revealed that most of those changes were independent of BGLF5. DFLR and DFLR BGLF5-knockout (dBGLF5) LCLs induced into lytic EBV replication were FAC-sorted and RNA-sequenced (5 and 3 biological replicates, respectively) to characterize transcriptomic changes during early and late lytic phases and investigate BGLF5's role in host shutoff. Differential gene expression and alternative splicing/readthrough transcription were analyzed between latent and lytic fractions in WT and BGLF5-deficient LCLs.