Tetrandrine enhances the host antiviral response through cGAMP-mediated cGAS-STING signaling pathway
10.3760/cma.j.cn112309-20230411-00093
- VernacularTitle:粉防己碱通过cGAMP介导的cGAS-STING信号通路增强宿主的抗病毒反应
- Author:
Zhiwen WANG
1
;
Yaming ZHANG
;
Zhihui XIE
Author Information
1. 河南大学淮河医院医学检验科，开封 475000
- Keywords:
Tetrandrine;
cGAMP;
cGAS-STING signaling pathway;
Herpes simplex virus typeⅠ
- From:
Chinese Journal of Microbiology and Immunology
2024;44(1):17-26
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether tetrandrine could be used as an agonist of cGAMP to enhance the activation of cGAS-STING signaling pathway and analyze the antiviral function of tetrandrine.Methods:THP1-Lucia-ISRE and RAW-Lucia-ISRE cells were incubated with different doses of tetrandrine in combination with cGAMP, respectively. IRF3 reporter activity was analyzed by luciferase reporter assay. Western blot was used to detect the activation of cGAS-STING signaling pathway. The expression of IFN-β, CXCL10 and CCL5 at mRNA level was quantified by real-time quantitative PCR. The expression of IFN-β at protein level was assessed by ELISA. HeLa cells stably expressing STING-GFP gene (HeLa-STNG-GFP cells) were constructed and stimulated with tetrandrine and cGAMP, then puncta-like structures were imaged by ZEISS LSM780. THP1-Lucia-ISRE cells were infected with herpes simplex virus type 1 (HSV-1) in the presence or absence of tetrandrine or cGAMP. The antiviral function of tetrandrine was analyzed by Western blot and fluorescence intensity assay.Results:Tetrandrine enhanced cGAMP-mediated IRF3 responses and activated cGAS-STING signaling pathway in combination with cGAMP. Tetrandrine combined with cGAMP triggered STING translocation and the formation of puncta-like structures in HeLa-STNG-GFP cells. The titer of HSV-1, the expression of HSV-glycoprotein D/UL30 and the fluorescence intensity of HSV-GFP were all decline after treating HSV-1-infected THP1-Lucia-ISRE cells with tetrandrine and cGAMP.Conclusions:Tetrandrine combined with cGAMP activates cGAS-STING signaling pathway, thus enhancing the host antiviral response.
