Activation of PD-1/PD-L1 immune checkpoint by Zika virus

Chenxi Wang, Yubin Xie, Weixin Li, Chon Phin Ong, Hao Ding, Shuofeng Yuan, Gong Cheng, Dong-Yan Jin and Zi-Wei Ye

PLOS Pathogens, 2025, vol. 21, issue 9, 1-22

Abstract: Zika virus (ZIKV) has emerged as a rising concern in global health in recent years. The role of PD-1/PD-L1 immune checkpoint in acute ZIKV infection remains to be understood. In this study we demonstrated the activation of PD-1/PD-L1 immune checkpoint by ZIKV. mRNA and protein expression of PD-L1 was boosted by ZIKV not only in SF268 and JEG3 cell lines but also in human dendritic cells. PD-1 expression was more abundant on CD8+ T cells in ZIKV-infected mice. Elevated PD-L1 expression was also observed in the brain, testis and spleen of ZIKV-infected A129 mice. Blocking PD-L1 effectively inhibited ZIKV infection, reducing viral loads in all tissues. In addition, anti-PD-L1 antibody treatment further increased virus-specific CD8+ T cells, KLRG+ CD8+ T cells, and effector memory CD8+ T cells. PD-L1 blockade also induced interferon γ, granzyme B, and interleukin 2 expression in antigen-specific CD8+ T cells, consistent with activation of these cells. Mechanistically, the induction of PD-L1 expression might be ascribed to viral NS4B protein and its interaction with GRP78. Our findings suggest that targeting the PD-1/PD-L1 pathway could have antiviral effect against ZIKV.Author summary: Immune checkpoint blockade has become another pillar in cancer treatment, but whether the same strategy might be used in antiviral therapy remains to be clarified. In this study we used ZIKV infection as an example to understand immune checkpoint activation during acute infection. The activation of the PD-1/PD-L1 immune checkpoint by ZIKV was demonstrated by several lines of evidence. Blocking this checkpoint using anti-PD-L1 antibodies effectively inhibited ZIKV infection in mice, reducing viral burdens in all tissues, consistent with enhanced virus-specific T cell response. It was further found that the ability to induce PD-L1 expression would be ascribed to one viral protein named NS4B and its interaction with another cellular protein GRP78. Our work revealed a new antiviral strategy against ZIKV by blocking the PD-1/PD-L1 immune checkpoint.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013457 (text/html)
https://journals.plos.org/plospathogens/article/fi ... 13457&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:ppat00:1013457

DOI: 10.1371/journal.ppat.1013457

Access Statistics for this article

More articles in PLOS Pathogens from Public Library of Science
Bibliographic data for series maintained by plospathogens ().