TY - JOUR
T1 - PD-L1 upregulation by lytic induction of Epstein-Barr Virus
AU - Yanagi, Yusuke
AU - Hara, Yuya
AU - Mabuchi, Seiyo
AU - Watanabe, Takahiro
AU - Sato, Yoshitaka
AU - Kimura, Hiroshi
AU - Murata, Takayuki
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/3
Y1 - 2022/3
N2 - Epstein-Barr virus (EBV) is an etiologic agent of infectious mononucleosis and several malignancies. Here, we found that reactivation of EBV resulted in increased programmed cell death-ligand 1 (PD-L1) expression in a cell type-dependent manner. Lytic induction in EBV-positive Akata, AGS, MutuI, and Jijoye cell lines increased PD-L1 levels, but cells such as EBV-negative Akata, MutuIII, and P3HR1 did not have increased PD-L1. EBV in the P3HR1 cell line has a deletion in the EBNA2 gene, while EBV in its parental cell line, Jijoye, has the complete EBNA2 gene. PD-L1 expression by lytic induction was reduced when EBNA2 was knocked down. In addition, pharmacological inhibition indicated involvement of nuclear factor kappa B, mitogen-activated protein kinase, and AKT signaling. These results suggest that EBV likely evades immunity by inducing PD-L1 upon reactivation, through the increased expression of EBNA2 and activation of signaling pathways.
AB - Epstein-Barr virus (EBV) is an etiologic agent of infectious mononucleosis and several malignancies. Here, we found that reactivation of EBV resulted in increased programmed cell death-ligand 1 (PD-L1) expression in a cell type-dependent manner. Lytic induction in EBV-positive Akata, AGS, MutuI, and Jijoye cell lines increased PD-L1 levels, but cells such as EBV-negative Akata, MutuIII, and P3HR1 did not have increased PD-L1. EBV in the P3HR1 cell line has a deletion in the EBNA2 gene, while EBV in its parental cell line, Jijoye, has the complete EBNA2 gene. PD-L1 expression by lytic induction was reduced when EBNA2 was knocked down. In addition, pharmacological inhibition indicated involvement of nuclear factor kappa B, mitogen-activated protein kinase, and AKT signaling. These results suggest that EBV likely evades immunity by inducing PD-L1 upon reactivation, through the increased expression of EBNA2 and activation of signaling pathways.
KW - EBNA2
KW - EBV
KW - Lytic reactivation
KW - PD-L1
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U2 - 10.1016/j.virol.2022.01.006
DO - 10.1016/j.virol.2022.01.006
M3 - Article
C2 - 35093708
AN - SCOPUS:85123604723
SN - 0042-6822
VL - 568
SP - 31
EP - 40
JO - Virology
JF - Virology
ER -