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Updated: Jan 18, 2026
Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Activation of PD-1/PD-L1 immune checkpoint by Zika virus
Chenxi Wang1, Yubin Xie2, Weixin Li1
1School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
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.
Insights
Zika virus (ZIKV) activates the PD-1/PD-L1 immune checkpoint. Blocking this pathway with anti-PD-L1 antibodies reduced viral loads and enhanced anti-ZIKV T cell responses, suggesting a potential antiviral strategy.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Zika virus (ZIKV) poses a significant global health threat.
- The role of the PD-1/PD-L1 immune checkpoint in ZIKV infection is not well understood.
Purpose of the Study:
- To investigate the impact of ZIKV infection on the PD-1/PD-L1 immune checkpoint.
- To evaluate the therapeutic potential of targeting the PD-1/PD-L1 pathway against ZIKV.
Main Methods:
- Assessed PD-L1 mRNA and protein expression in ZIKV-infected cell lines and human dendritic cells.
- Analyzed PD-1 expression on T cells in ZIKV-infected mice.
- Measured viral loads and immune cell populations in mice treated with anti-PD-L1 antibodies.
Main Results:
- ZIKV infection upregulated PD-L1 expression in various cell types and tissues.
- PD-1 expression increased on CD8+ T cells in infected mice.
- Anti-PD-L1 treatment reduced ZIKV viral loads and boosted virus-specific CD8+ T cell responses, including effector memory cells.
- PD-L1 blockade promoted the production of cytokines like interferon-gamma and interleukin-2.
Conclusions:
- ZIKV infection activates the PD-1/PD-L1 immune checkpoint.
- Targeting the PD-1/PD-L1 pathway demonstrates antiviral effects against ZIKV.
- This pathway represents a promising therapeutic target for ZIKV infection.
