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Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction
Liu, Yu Xu, Xi-Qiu Li, Wei-Jing Zhang, Biao Meng, Feng-Zhen Wang, Xu Majid, Safah M. Guo, Zihan Ho, Wen-Zhe
Liu, Yu
Xu, Xi-Qiu
Li, Wei-Jing
Zhang, Biao
Meng, Feng-Zhen
Wang, Xu
Majid, Safah M.
Guo, Zihan
Ho, Wen-Zhe
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Journal article
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2024-05-13
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Pathology and Laboratory Medicine
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https://doi.org/10.3389/fcimb.2024.1383811
Abstract
Introduction: While astrocytes participate in the CNS innate immunity against herpes simplex virus type 1 (HSV-1) infection, they are the major target for the virus. Therefore, it is of importance to understand the interplay between the astrocyte-mediated immunity and HSV-1 infection.Methods: Both primary human astrocytes and the astrocyte line (U373) were used in this study. RT-qPCR and Western blot assay were used to measure IFNs, the antiviral IFN-stimulated genes (ISGs), IFN regulatory factors (IRFs) and HSV-1 DNA. IRF1 knockout or knockdown was performed with CRISPR/Cas9 and siRNA transfection techniques.Results: Poly(dA:dT) could inhibit HSV-1 replication and induce IFN-β/IFN-λs production in human astrocytes. Poly(dA:dT) treatment of astrocytes also induced the expression of the antiviral ISGs (Viperin, ISG56 and MxA). Among IRFs members examined, poly(dA:dT) selectively unregulated IRF1 and IRF9, particularly IRF1 in human astrocytes. The inductive effects of poly(dA:dT) on IFNs and ISGs were diminished in the IRF1 knockout cells. In addition, IRF1 knockout attenuated poly(dA:dT)-mediated HSV-1 inhibition in the cells.Conclusion: The DNA sensors activation induces astrocyte intracellular innate immunity against HSV-1. Therefore, targeting the DNA sensors has potential for immune activation-based HSV-1 therapy.
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Liu Y, Xu X-Q, Li W-J, Zhang B, Meng F-Z, Wang X, Majid SM, Guo Z and Ho W-Z (2024) Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction. Front. Cell. Infect. Microbiol. 14:1383811. doi: 10.3389/fcimb.2024.1383811
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Frontiers in Cellular and Infection Microbiology, Vol. 14
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