TY - JOUR
T1 - RNAseq analysis identifies involvement of EBNA2 in PD-L1 induction during Epstein-Barr virus infection of primary B cells
AU - Yanagi, Yusuke
AU - Okuno, Yusuke
AU - Narita, Yohei
AU - Masud, H. M.Abdullah Al
AU - Watanabe, Takahiro
AU - Sato, Yoshitaka
AU - Kanda, Teru
AU - Kimura, Hiroshi
AU - Murata, Takayuki
N1 - Funding Information:
This work was supported by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology ( 19K07580 to T.M., 19K22560 and 20H03493 to H.K.), Japan Agency for Medical Research and Development (AMED) ( JP20wm0325012 to T.M., JP19jk0210023 to Y.S.), the Takeda Science Foundation (to T.M.), and the Hori Sciences and Arts Foundation (to T.M. Y.S. and H.K.), the General Assembly of the Japanese Association of Medical Sciences (to T.M.). We thank Drs. B. Zhao, W. Hammerschmidt, H. J. Delecluse, H. Yoshiyama, and T. Tsurumi for materials and discussions.
Publisher Copyright:
© 2021
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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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U2 - 10.1016/j.virol.2021.02.004
DO - 10.1016/j.virol.2021.02.004
M3 - Article
C2 - 33639481
AN - SCOPUS:85101366232
VL - 557
SP - 44
EP - 54
JO - Virology
JF - Virology
SN - 0042-6822
ER -