A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth

Epstein-Barr virus (EBV) immortalizes resting human B lymphocytes in vitro through expression of viral transcription factors (TFs). These viral TFs activate the expression of key oncogenes, many through long-range enhancer looping. Here we combined various chromatin conformation capture related methods (HiC, HiChIP, 4C-seq etc) to systematically evaluate the effect of EBV infection on host genome-wide 3D organization. HiC was performed on resting B cells to recapticulate the 3D chromatin feature before EBV infection and transformation. A time-course RNA-seq was performed to track the dynamics of viral infection of resting B cells. Next, HiChIP was performed on conditional cells for the viral TF, EBNA3A, to understand how it rewires the host nucleus, particular enhancer-promoter interactions. In addition, HiChIP for RNA Polymerase II was also performed on primary B cells at Day 0 and Day 28 after EBV infection. Finally, 4C-seq was performed on conditional cells for the viral TF, EBNA3C, to understand how it modulates host chromatin interactions at the CDKN2A and AID loci. Please note that the peak data (for GSM5456429-GSM5456440) are generated from both replicates and is linked to the corresponding *rep1 sample records.