%0 Journal Article
%T Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction.
%A Liu Y
%A Xu XQ
%A Li WJ
%A Zhang B
%A Meng FZ
%A Wang X
%A Majid SM
%A Guo Z
%A Ho WZ
%J Front Cell Infect Microbiol
%V 14
%N 0
%D 2024
%M 38808062
%F 6.073
%R 10.3389/fcimb.2024.1383811
%X <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.