RNAseq analysis identifies involvement of EBNA2 in PD-L1 induction during Epstein-Barr virus infection of primary B cells
2021
Yanagi, Yusuke | Okuno, Yusuke | Narita, Yohei | Masud, H.M Abdullah Al | Watanabe, Takahiro | Satō, Yoshitaka | Kanda, Teru | Kimura, Hiroshi | Murata, Takayuki
Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and several types of malignancy. RNAseq of peripheral blood primary B cell samples infected with wild-type EBV revealed that expression of programmed cell death ligand-1 (PD-L1) is markedly induced by infection. This induction of PD-L1 was alleviated by knockout of the EBNA2 gene, but knockout of LMP1 had little effect. ChIPseq, ChIA-PET, and reporter assays further confirmed that EBNA2-binding sites in the promoter region and at 130 kb downstream of the PD-L1 gene played important roles in PD-L1 induction. Our results indicate that EBV mainly utilizes the EBNA2 gene for induction of PD-L1 and to evade host immunity on infection of primary B cells. Furthermore, pathway analysis revealed that genes involved in the cell cycle, metabolic processes, membrane morphogenesis, and vesicle regulation were induced by EBNA2, and that EBNA2 suppressed genes related to immune signaling.
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