INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2025
·Vol. 26
·期 23
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IF 4.9
Huiqiang Wang,Ya Wang,Shuo Wu,Lijun Qiao,Wen Sheng,Haiyan Yan,Kun Wang,Ge Yang,Jiandong Jiang,Yuhuan Li
Previous studies have reported that Enterovirus A71 (EV-A71) infection could activate STING-related signaling pathways in vitro, but the role of STING in EV-A71 infection in vivo and the associated immune regulatory mechanisms remain unclear. Here, we used the STING-specific agonist diABZI to activate STING and STING-knockout mice to jointly study the role and mechanism of regulating STING on EV-A71 infection in vivo. The results showed that activating STING could inhibit the in vivo replication of EV-A71, alleviate clinical symptoms in infected mice, and increase the survival rate. Conversely, STING knockout significantly promoted viral replication in vivo and increased the lethality and severity of EV-A71 infection. Mechanistic studies further revealed that STING activation exerts its antiviral effects by stimulating interferon signaling pathways, upregulating the expression of interferon-stimulated genes (ISGs). Additionally, STING activation also modulated the serum cytokine response profile. Moreover, STING activation drove the expansion of diverse immune cell populations, including T cells, natural killer (NK) cells and myeloid cells. In contrast, STING knockout not only reduced the proportion of thymic T cells and impeded T cell developmental progression from double-positive (DP) to single-positive (SP) stages, but also impaired the effector functions of CD8+ T cells and NK cells during viral infection. In summary, this study demonstrates that STING activation effectively suppresses EV-A71 replication and mitigates infection symptoms by modulating immune and inflammatory responses. These findings provide a foundational framework for understanding how STING coordinates antiviral immunity and inform future investigations into STING-targeted therapies for viral infections.
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PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2021
·
IF 10.618
Jiasheng Yuan,Jiayin Shen,Mingyu Chen,Zhichao Lou,Shuye Zhang,Zhigang Song,Weiwei Li,Xin Zhou
Direct visual enumeration of viruses under dark-field microscope (DFM) using plasmon resonance probes (PRPs) is fast and convenient; however, it is greatly limited in the assay of real samples because of its inability to accurately identify false positives owing to non-specific adsorption. In this study, we propose an artificial intelligence (AI)-assisted DFM enumeration strategy for the accurate assay of Enterovirus A71 (an ultra-small human virus) using two PRPs; a 40 nm silver nanoparticle probe (SNP) that appears bright blue under DFM, and a 120 nm gold nanorod probe (GNP) that appears red under DFM. The capture chip was prepared by immobilizing the SNPs with antibodies on the glass to capture the target virus and to form dichromatic sandwich structures with the GNPs, followed by imaging under a dark field (DF). Subsequently, the DF images of the capture chip were subjected to a two-step screening: first, using image processing , and thereafter using the AI algorithm screening to eliminate false positive results and background noise. The results revealed that the data from the AI-assisted dual PRPs assay were highly consistent with those of quantitative PCR (qPCR), and that the sensitivity with a minimum detectable concentration of 3 copies/μL was 5 times higher than that of qPCR. The entire analysis was completed within 45 min. Therefore, our AI-assisted virus enumeration strategy with two DF PRPs holds great potential for ultra-sensitive and accurate quantification of viruses in real samples.
研究领域:
病毒学
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纳米技术
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人工智能
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医学诊断
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高影响因子
PROTEOMICS
·
2022
·Vol. 23
·期 2
·2200362
·
IF 5.393
Huichun Shi,Siyuan Liu,Zhimi Tan,Lin Yin,Liyan Zeng,Tiefu Liu,Shuye Zhang,Lijun Zhang
Enterovirus A71 (EV71) infection can cause hand, foot, and mouth disease (HFMD) and severe neurological complications in children. However, the biological processes regulated by EV71 remain poorly understood. Herein, proteomics and metabonomics studies were conducted to uncover the mechanism of EV71 infection in rhabdomyosarcoma (RD) cells and identify potential drug targets. Differential expressed proteins from enriched membrane were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics technology. Twenty-six differential proteins with 1.5-fold ( p < 0.05) change were detected, including 14 upregulated proteins and 12 downregulated proteins. The upregulated proteins are mainly involved in metabolic process, especially in the glycolysis pathway. Alpha-enolase (ENO1) protein was found to increase with temporal dependence following EV71 infection. The targeted metabolomics analysis revealed that glucose absorption and glycolysis metabolites were increased after EV71 infection. The glycolysis pathway was inhibited by knocking down ENO1 or the use of a glycolysis inhibitor (dichloroacetic acid [DCA]); and we found that EV71 infection was inhibited by depleting ENO1 or using DCA. Our study indicates that EV71 may reprogram glucose metabolism by activating glycolysis, and EV71 infection can be inhibited by interrupting the glycolysis pathway. ENO1 may be a potential target against EV71, and DCA could act as an inhibitor of EV71.
研究领域:
病毒学
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蛋白质组学
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代谢组学
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分子生物学
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细胞生物学
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传染病学
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高影响因子
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