VIROLOGICA SINICA
·
2012
·Vol. 27
·期 1
·19-25
·
IF 0
Liang Yuan-Yuan,Wang Bin,Qian Dong-Meng,Li Ling,Wang Zhi-Hao,Hu Ming,Song Xu-Xia
To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1(HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRb1, GRb1+HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRb1 on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 μg/mL GRb1 and 400 μg/mL GRb1+HSV-1 groups, MTT values were higher than control group at all times ( P <0. 05). Moreover, the apoptosis rate in the 400 μg/mL GRb1+HSV-1 group was lower than the HSV-1 group ( P <0. 05). These results confirmed that, at appropriate concentrations, GRb1 could inhibit nerve cell apoptosis in HSV-1 infections.
研究领域:
医学
·
病毒学
·
神经科学
·
药理学
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DOI
PubMed
Neuroscience Bulletin
·
2020
·Vol. 37
·期 5
·701-719
·
IF 4.326
Yang Hong,Xiong Feng,Song Yi-Ge,Jiang Hai-Fei,Qin Hai-Bin,Zhou Jing,Lu Sha,Grieco Steven F.,Xu Xiangmin,Zeng Wen-Bo,Zhao Fei,Luo Min-Hua
Anterograde viral tracers are powerful and essential tools for dissecting the output targets of a brain region of interest. They have been developed from herpes simplex virus 1 (HSV-1) strain H129 (H129), and have been successfully applied to map diverse neural circuits. Initially, the anterograde polysynaptic tracer H129-G4 was used by many groups. We then developed the first monosynaptic tracer, H129-dTK-tdT, which was highly successful, yet improvements are needed. Now, by inserting another tdTomato expression cassette into the H129-dTK-tdT genome, we have created H129-dTK-T2, an updated version of H129-dTK-tdT that has improved labeling intensity. To help scientists produce and apply our H129-derived viral tracers, here we provide the protocol describing our detailed and standardized procedures. Commonly-encountered technical problems and their solutions are also discussed in detail. Broadly, the dissemination of this protocol will greatly support scientists to apply these viral tracers on a large scale.
研究领域:
神经科学
·
病毒学
·
分子生物学
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DOI
PubMed
高影响因子
NATURE IMMUNOLOGY
·
2020
·Vol. 21
·期 7
·727-735
·
IF 20.479
Jia Mutian,Qin Danhui,Zhao Chunyuan,Chai Li,Yu Zhongxia,Wang Wenwen,Tong Li,Lv Lin,Wang Yuanyuan,Rehwinkel Jan,Yu Jinming,Zhao Wei
Stimulator-of-interferon genes (STING) is vital for sensing cytosolic DNA and initiating innate immune responses against microbial infection and tumors. Redox homeostasis is the balance of oxidative and reducing reactions present in all living systems. Yet, how the intracellular redox state controls STING activation is unclear. Here, we show that cellular redox homeostasis maintained by glutathione peroxidase 4 (GPX4) is required for STING activation. GPX4 deficiency enhanced cellular lipid peroxidation and thus specifically inhibited the cGAS–STING pathway. Concordantly, GPX4 deficiency inhibited herpes simplex virus-1 (HSV-1)-induced innate antiviral immune responses and promoted HSV-1 replication in vivo. Mechanistically, GPX4 inactivation increased production of lipid peroxidation, which led to STING carbonylation at C88 and inhibited its trafficking from the endoplasmic reticulum (ER) to the Golgi complex. Thus, cellular stress–induced lipid peroxidation specifically attenuates the STING DNA-sensing pathway, suggesting that GPX4 facilitates STING activation by maintaining redox homeostasis of lipids.
研究领域:
免疫学
·
细胞生物学
·
病毒学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yaxiu Feng,Xiong Wang,Cien Chen,Di Wang,Changshun Hou,Yiran Wang,Huan Hu,Peiran Chen,LeiYing Qin,Qianya Wan,Xi Yao,Ming-Liang He
Incurable infection by herpes simplex virus 1 (HSV-1) can cause severe encephalitis and neurodegenerative diseases, e.g., Alzheimer's disease (AD) and amyotrophic lateral sclerosis. How HSV-1 reaches the brain from the initial infection site remains inconclusive. Here, an innovative approach combining carbon quantum dots (CQDs) with dissolving microneedles (dMN) for real-time tracking of HSV-1 from skin to brain is presented. Upon application, CQDs-HSV-1 is released from the dMN through the swelling of interstitial fluid (ISF) in skin and subsequently monitored by living imaging. Remarkably, it is observed that HSV-1 preferentially infects peripheral skin nerves, almost all viruses directly enter to brain via the spinal cord within 10–30 min, while few viruses enter the brain through the bloodstream via tail vein injection at the same time. Spinal cord injury (SCI) significantly delays the HSV-1 transport from skin to brain but has no effect on the virus's travel from blood to brain. In a microfluid system, HSV-1 shows preferential neurite infection, then transports to the cell body of differentiated SH-SY5Y cells, highlighting the viral traffic process in neurons. The integration of CQDs-virus labelling technology and dMN delivery model presents a promising tool for investigating the in vivo transport routes of neurotropic viruses with initial skin infections.
研究领域:
病毒学
·
生物医学工程
·
神经科学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-12
·
IF 16.6
Jia Mutian,Wang Yuanyuan,Wang Jie,Qin Danhui,Wang Mengge,Chai Li,Fu Yue,Zhao Chunyuan,Gao Chengjiang,Jia Jihui,Zhao Wei
Stimulator of interferon gene (STING)-triggered autophagy is crucial for the host to eliminate invading pathogens and serves as a self-limiting mechanism of STING-induced interferon (IFN) responses. Thus, the mechanisms that ensure the beneficial effects of STING activation are of particular importance. Herein, we show that myristic acid, a type of long-chain saturated fatty acid (SFA), specifically attenuates cGAS-STING-induced IFN responses in macrophages, while enhancing STING-dependent autophagy. Myristic acid inhibits HSV-1 infection-induced innate antiviral immune responses and promotes HSV-1 replication in mice in vivo. Mechanistically, myristic acid enhances N-myristoylation of ARF1, a master regulator that controls STING membrane trafficking. Consequently, myristic acid facilitates STING activation-triggered autophagy degradation of the STING complex. Thus, our work identifies myristic acid as a metabolic checkpoint that contributes to immune homeostasis by balancing STING-dependent autophagy and IFN responses. This suggests that myristic acid and N-myristoylation are promising targets for the treatment of diseases caused by aberrant STING activation.
研究领域:
免疫学
·
细胞生物学
·
病毒学
·
代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Weikang Sun,Renjie Luo,Qingwei Qu,Jie Yang,Guang Yang,Lihua Song,Peng Cao,Erguang Li
Plant-based phenolic components and their metabolites, such as ellagic acid (EA) and urolithin A (UA), possess a variety of biological activities. Here, we investigated the antiviral effect of EA and UA against HSV-1 infection, a virus that causes peripheral infection as well as brain inflammation. Both compounds demonstrated potent antiviral activity. Network pharmacology and molecular docking analyses identified protein kinase CK2 as a common target for their action. We showed that both EA and UA were direct CK2 inhibitors using an enzymatic assay, an observation substantiated in cell culture studies. The effect of EA and UA on HSV-1 infection through CK2 was confirmed in CK2 (CSNK2B) knockout cells. Finally, we demonstrated an antiviral effect using a murine model of herpetic stromal keratitis. EA or UA treatment reduced HSV-1 shedding and prevented viral neuroinvasion. CK2 is a critical enzyme involved in cell proliferation and the proinflammatory response. In addition to identifying CK2 as a putative target of EA and UA antiviral activities, this study also demonstrates that EA and its metabolite UA have the potential to reduce infection-associated neurodegenerative inflammation.
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Hao Guo,Xinhuan Wan,Fengju Niu,Jujie Sun,Chenxiao Shi,Jessica Meng Ye,Changzheng Zhou
In this study, we aimed to evaluate the antiviral effect of total flavonoids extracted from Robinia pseudoacacia cv. idaho (RPTF) in vivo and its toxicity on rats with oral gavage. RPTF was prepared by percolation with 70% ethanol for 24 h and its antiviral effect on different kinds of viruses was evaluated in vitro by MTT staining. The long-term toxicity of RPTF on rats was evaluated through the detection of general behavior, body weight, food intake and related organ tissue sections of experimental animals. We found that RPTF produced significantly inhibitory effects on HSV-1 and EV-71 viruses with the therapeutic index TI values 113.8 and 46.2, respectively. Moreover, toxicity evaluation in vivo showed no significantly adverse effects in rats, indicating that RPTF was safe in use. In conclusion, we demonstrated that RPTF, natural compounds in the Chinese traditional medicine, could act as promising and effective antiviral therapeutics with relative safety in use.
研究领域:
药理学
·
病毒学
·
毒理学
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2025
·Vol. 15
·期 1
·159
·
IF 6.2
Sun Weikang,Zhang Mengyu,Wang Ruilin,Yang Jie,Rasool Ameena Tur,Luo Renjie,Liu Xiangdong,Cao Peng,Li Erguang
Background The RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), also known as heterogeneous nuclear ribonucleoprotein I (hnRNP I), mediates gene expression through splicing regulation. Its role in virus infection is undefined. Results We show that genetic ablation of PTBP1 renders cell resistant to herpes simplex virus 1 (HSV-1) infection. HSV-1 utilizes 3-O-sulfated heparan sulfate proteoglycans (HSPGs) for attachment and for infection of epithelial cells. We found that knockout of PTBP1 expression resulted in loss of HS3ST3A1 and HS3ST3B1, heparan sulfate glucosaminyl 3-O-sulfotransferase genes for 3-O-sulfation of the heparan sulfate (HS) chains of HSPGs. Each of the HS3ST3A1/HS3ST3B1 genes is composed of 2 exons separated by an extraordinarily long intron whose removal requires PTBP1-associated looping. We found that PTBP1 interacted with the intronic region of HS3ST3A1/HS3ST3B1 pre-mRNAs and modulated their processing to mRNA. The essential role of PTBP1 in functional HS3ST3A1 expression and in HSV-1 infection was demonstrated by ectopic re-expression in the knockout (ko) cells. In addition, we showed that targeting PTBP1 expression by microRNA mimics reduced disease symptoms in a mouse herpetic stromal keratitis (HSK) model. Conclusions The results demonstrate that PTBP1 mediates HSV-1 infection of epithelial cells through splicing regulation of HS3ST3A1/HS3ST3B1. These studies provide a new area for novel therapeutic strategies through splicing regulation. Graphical abstract By Sun et al. RNA-binding protein PTBP1 mediates HSV-1 attachment and infection through regulation of heparan sulfate 3-O-sulfotransferase gene expression.
研究领域:
分子生物学
·
病毒学
·
细胞生物学
·
基因表达调控
·
RNA剪接
·
感染免疫
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眼科学
·
转化医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2020
·
IF 4.858
Yiliang Wang,Lianzhou Huang,Yun Wang,Weisheng Luo,Feng Li,Ji Xiao,Shurong Qin,Zhaoyang Wang,Xiaowei Song,Yuan Wang,Fujun Jin,Yifei Wang
Herpes simplex virus (HSV) type 1 (HSV-1) infection exhibited high heterogeneity at individual cells level, including the different gene expression patterns and varying amounts of progeny virus. However, the underlying mechanism of such variability remains obscure. The importance of host long noncoding RNAs (lncRNAs) in virus infection had been recognized, while the contribution of lncRNAs to the heterogeneous infection remains unknown. Herein, a prior single-cell RNA sequencing data using HSV-1 reporter strain expressing ICP4-YFP was re-analyzed to obtain the differentially expressed lncRNA between the successfully initiated viral gene expression (ICP4-YFP + ) cells and the aborted infection cells (ICP4-YFP - ). The ICP4-YFP + population show a higher abundance of MAMDC2 antisense 1 (MAMDC2-AS1) lncRNA than ICP4-YFP - population. MAMDC2-AS1 silencing reduces the expression of HSV-1 immediate early (IE) genes and limit HSV-1 infection in human host cells. Consistently, ectopic expression of MAMDC2-AS1 enhances HSV-1 IE genes transcription and facilitates the formation of HSV-1-induced plaques. Mechanically, both RNA-pull down and RNA immunoprecipitation assays show that MAMDC2-AS1 interacts with the RNA binding protein heat shock protein 90α (Hsp90α), a molecular chaperone involving in the nuclear import of HSV-1. The MAMDC2-AS1-Hsp90α interaction facilitates the nuclear transport of viral tegument protein VP16, the core factor initiating the expression of HSV-1 IE genes. The transcription factor YY1 mediates the induction of MAMDC2-AS1 upon HSV-1 infection. Our study elucidates the contribution of lncRNA to HSV-1 infection susceptibility in human cells and the role of Hsp90α RNA binding activity in HSV-1 infection.
研究领域:
病毒学
·
分子生物学
·
细胞生物学
·
基因组学
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DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2025
·
IF 3.9
Weikang Sun,Ke Ren,Jingjing Li,Mengyu Zhang,Qishen Jiang,Lingling Wang,Erguang Li
(199 words) The c-Jun N-terminal kinase (JNK) signaling pathway is required for herpes simplex virus 1 lytic infection and reactivation from latency. JNK signaling regulates cellular processes in response to stress through transcriptional regulation. However, the mechanisms by which JNK regulates HSV-1 infection are less defined. We show here that HSV-1 infection triggers BRD4 transition from chromosome association to transcriptional regulation for viral infection. Specifically, HSV-1 infection induces JNK activation which mediates redistribution of BRD4, an epigenetic reader protein, from chromatin-targeting to association with proteins of transcriptional regulation. BRD4 transitions to viral infection regulation by complexing with P-TEFb, a positive transcription elongation factor, and association with viral DNA. Genetic ablation or perturbation of JNK with chemical inhibitors or siRNA leads to impediment of BRD4 release and inhibition of HSV-1 infection. Both chemotherapeutic agents and irradiation are known to promote JNK activation and HSV reactivation. We show further that JNK agonist or chemotherapeutic agents known to activate JNK have the ability to enhance HSV-1 infection. Our study reveals a novel mechanism by which JNK regulates HSV-1 infection through stress-induced BRD4 function transition from host chromosome association to viral gene expression. The work links recurrent HSV infection by chemotherapeutic agents to JNK activation.
研究领域:
病毒学
·
分子生物学
·
细胞信号传导
·
表观遗传学
·
转录调控
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DOI
PubMed
高影响因子
ACS Sensors
·
2025
·
IF 9.1
Mengqi Huang,Kunte Shang,Luyi Ying,Yuqi Han,Ningxi Hong,Yu-Feng Yao
Rapid and precise detection of specific DNA is valuable for biological research and clinical disease diagnosis. Clustered regularly interspaced short palindromic repeat (CRISPR) technology can enhance existing DNA testing, making DNA detection faster, more portable, and more accurate. This study presents a new Cas12-driven exponential amplification-based lateral flow biosensor (CADEX-LF) for rapid and highly sensitive DNA detection. CADEX-LF takes full advantage of the highly specific target-loading-dependent trans-cleavage activity of Cas12 and the extremely high efficiency of nicking endonuclease-mediated exponential amplification. The adoption of lateral flow readout enables CADEX-LF for point-of-care (POC) use without requiring complicated supplementary equipment. CADEX-LF was shown to achieve a detection sensitivity of 2 × 10–15 M within 45 min of measurement time and displayed outstanding specificity with double-base resolution. Furthermore, CADEX-LF could identify herpes simplex virus 1 (HSV-1) DNA in tears of rabbits and clinical patients with HSV-1 keratitis, exhibiting its practical application potential in clinical diagnosis. The proposed CADEX-LF biosensor may have great promise for point-of-care disease diagnosis in resource-limited environments.
研究领域:
分子生物学
·
临床诊断学
·
生物传感器技术
·
病毒学
·
精准医学
·
转化医学
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产品关联
DOI
PubMed
高影响因子
Molecular Therapy-Oncolytics
·
2023
·
IF 5.7
Jun Xie,Shaowei Wang,Yunhong Zhong,Ming Gao,Xuezhang Tian,Liting Zhang,Dongli Pan,Qingsong Qin,Bing Wu,Ke Lan,Zhi-Jun Sun,Junjie Zhang
Oncolytic viruses (OVs) encoding various transgenes are being evaluated for cancer immunotherapy. Diverse factors such as cytokines, immune checkpoint inhibitors, tumor-associated antigens, and T cell engagers have been exploited as transgenes. These modifications are primarily aimed to reverse the immunosuppressive tumor microenvironment. By contrast, antiviral restriction factors that inhibit the replication of OVs and result in suboptimal oncolytic activity have received far less attention. Here, we report that guanylate-binding protein 1 (GBP1) is potently induced during HSV-1 infection and restricts HSV-1 replication. Mechanistically, GBP1 remodels cytoskeletal organization to impede nuclear entry of HSV-1 genome. Previous studies have established that IpaH9.8, a bacterial E3 ubiquitin ligase, targets GBPs for proteasomal degradation. We therefore engineered an oncolytic HSV-1 to express IpaH9.8 and found that the modified OV effectively antagonized GBP1, replicated to a higher titer in vitro and showed superior antitumor activity in vivo . Our study features a strategy for improving the replication of OVs via targeting a restriction factor and achieving promising therapeutic efficacy.
研究领域:
肿瘤学
·
病毒学
·
免疫疗法
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
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