PD-L1 upregulation by lytic induction of Epstein-Barr Virus.

Authors :: Yanagi Y
Hara Y
Mabuchi S
Watanabe T
Sato Y
Kimura H
Murata T
Source :: Virology [Virology] 2022 Mar; Vol. 568, pp. 31-40. Date of Electronic Publication: 2022 Jan 20.
Publication Year :: 2022
Abstract: 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.<br /> (Copyright © 2022 Elsevier Inc. All rights reserved.)