ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
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2023
·Vol. 67
·期 3
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IF 4.9
Oluwatayo Israel Olasunkanmi,Yanru Fei,Juval Avala Ntsigouaye,Ming Yi,Yao Wang,Jinchang Liu,Weixu Cheng,James Megeto,Tahira Bashir,Yang Chen,Weizhen Xu,Lexun Lin,Wenran Zhao,Yan Wang,Zhaohua Zhong
Enterovirus infections are life-threatening viral infections which occur mainly among children and are possible causes of viral outbreak. Until now, treatment and management of infections caused by members of the genus Enterovirus largely depended on supportive care, and no antiviral medications are currently approved for the treatment of most of these infections. The urgency of discovering new therapeutic options for the treatment of enterovirus infection is increasing. In the present study, we identified that trans-2-hexenoic acid (THA), a natural product from a dietary source, possesses antiviral activity against coxsackievirus B (CVB) and enterovirus A71 (EV-A71) in a dose-dependent manner. We found that THA possesses antiviral activity at 50% effective concentrations (EC50) of 2.9 μM and 3.21 μM against CVB3 and EV-A71 infections, respectively. The time of addition assay revealed that THA inhibits both CVB3 and EV-A71 replication at the entry stage of infection. Additional results from this study further suggest that THA inhibits viral replication by blocking viral entry. Given that THA has received approval as a food additive, treatment of enterovirus infections with THA might be a safe therapeutic option or could pave the way for semisynthetic manufacturing of more antiviral drugs in the future.
研究领域:
病毒学
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药理学
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传染病学
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DOI
PubMed
高影响因子
Biosafety and Health
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2020
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IF 0
Cong Jin,Bin Che,Zhengyuan Guo,Chuan Li,Yang Liu,Wei Wu,Shiwen Wang,Dexin Li,Zongqiang Cui,Mifang Liang
Ebola virus (EBOV) is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever. Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and spread. It has been known that EBOV virions bind to factors expressed at the host cell surface. Subsequently, the virions are internalized by a macropinocytosis-like process, followed by being trafficked through early and late endosomes. Recent researches indicate that the entry of EBOV into cells requires integrated and functional lipid rafts. Whilst lipid rafts have been hypothesized to play a role in virus entry, there is a current lack of supporting data. One major technical hurdle is the lack of effective approaches for observing viral entry. To provide evidence on the involvement of lipid rafts in the entry process of EBOV, we generated the fluorescently labeled Ebola virus like particles (VLPs), and utilized single-particle tracking (SPT) to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid rafts. In this study, we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process, and inform the essential function of lipid rafts for the entry of Ebola virus. As such, our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.
研究领域:
病毒学
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细胞生物学
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分子生物学
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感染性疾病
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生物医学成像
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DOI
EMBO REPORTS
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2025
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IF 6.2
Shuzhi Cui,Wei Gao,Yuxin Chen,Yi Xu,Zhifang Li,Yu Wei,Yaming Jiu
CDC42 is a member of Rho GTPase family that regulates various biological processes and its activity can be hijacked by invading pathogens. Here, we discovered that the level of active CDC42 in hepatocytes positively correlates with the entry capacity of hepatitis B virus (HBV). Mechanistically, CDC42 activation effectively promotes the transport of the viral receptor sodium taurocholate co-transporting polypeptide (NTCP) to the plasma membrane via Rab11 dependent recycling endosomal pathway. NTCP interacts with Rab11 and activation of CDC42 signaling reinforces the interaction between NTCP and Rab11. We further show that clathrin mediated endocytosis (CME), the known HBV entry pathway, is independent of CDC42 activity. Intriguingly, we reveal that CDC42 dependent macropinocytosis is a route for HBV entry, which is equally essential for viral infection as CME. Together, our findings uncover new mechanisms for HBV entry that involve unrecognized functions of CDC42 and suggest that Rho GTPase signaling might represent a potential target for antiviral therapy.
研究领域:
病毒学
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分子生物学
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细胞生物学
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感染性疾病
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肝脏病学
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信号转导
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药理学
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转化医学
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产品关联
DOI
PubMed
高影响因子
PLoS Pathogens
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2025
·Vol. 21
·期 9
·e1013481
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IF 4.9
Qian Wang,Zichao Peng,Bin Gui,Yongming Li,Lanjie Liao,Zuoyan Zhu,Yaping Wang,Libo He
Grass carp reovirus (GCRV) causes hemorrhagic disease and substantial economic losses in the aquaculture of grass carp ( Ctenopharyngodon idella ), a commercially important fish species in China. Although viral entry depends on interactions between viral proteins and host receptors, the specific host molecules mediating this process have not been fully elucidated. Here, we identify cell surface sialic acid (SA) as a critical functional receptor for GCRV. Enzymatic removal of SA markedly impaired viral attachment and infection. Competitive inhibition using SA-binding lectins or soluble SA confirmed that GCRV targets SA moieties on host cells. Genetic knockdown of SA biosynthesis attenuated viral binding and replication, whereas overexpression of SA pathway genes enhanced susceptibility. Surface plasmon resonance demonstrated direct binding between GCRV capsid proteins and soluble SA, and mutational analysis identified key amino acid residues involved. Notably, pretreatment of GCRV with soluble SA significantly improved fish survival and reduced virus-induced immune overactivation in vivo . To assess receptor specificity, parallel experiments using Rana grylio virus (RGV), a phylogenetically unrelated ranavirus , showed that RGV infection was unaffected by SA-targeted interventions, highlighting the specificity of SA utilization by GCRV. Together, these findings identify SA as a functional and specific receptor for GCRV, offering new insights into virus-host interactions and potential antiviral strategies in aquaculture.
Grass carp hemorrhagic disease, caused by grass carp reovirus (GCRV), poses a major threat to freshwater aquaculture in China. Despite extensive studies on GCRV, the identity of host cell receptors mediating viral entry remained unknown. In this study, we demonstrate that GCRV directly binds to sialic acids-sugar molecules commonly found on cell surfaces-to attach to and infect host cells. By using a combination of enzymatic removal, lectin blocking, genetic manipulation, and biochemical binding assays, we show that sialic acid is essential for GCRV attachment and infection. Furthermore, pre-incubating GCRV with soluble sialic acids significantly reduced infection in cultured cells and improved the survival of infected grass carp. These findings reveal a key mechanism of viral entry and suggest new strategies for disease prevention and selective breeding of resistant fish. Our study not only deepens understanding of aquareovirus biology but also provides practical insights for controlling viral outbreaks in aquaculture.
研究领域:
病毒学
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水产养殖
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分子生物学
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免疫学
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鱼类健康
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产品关联
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2025
·
IF 2.7
Qing Yang,Shengda Xie,Yundi Zhao,Xinxin Lin,Ning Wei,Miaolei Shi,Ruibing Cao
Japanese encephalitis virus (JEV) is a zoonotic pathogen that can be transmitted to humans and animals via arthropods, causing viral encephalitis. In this study, we investigated the role of transferrin receptor 1 (TfR1) in JEV infection. We found that knocking down TfR1 expression in A549 and HeLa cells significantly inhibited JEV entry, while overexpression of TfR1 in 293 T cells enhanced viral entry. The JEV E protein interacts with TfR1, specifically via the protease-like domain (residues 384–606). Additionally, the hTfR1 soluble ectodomain protein significantly blocked JEV infection in HeLa cells, and ferric ammonium citrate (FAC), an iron supplement, downregulated TfR1 expression and effectively inhibited JEV entry and infection. These findings identify TfR1 as an entry factor for JEV and a potential antiviral target, suggesting that small molecule inhibitors like FAC could offer a promising antiviral strategy.
研究领域:
病毒学
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分子生物学
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免疫学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Nature Protocols
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2022
·Vol. 18
·期 2
·458-489
·
IF 17.021
Liu Hao-Yang,Wang Zhi-Gang,Liu Shu-Lin,Pang Dai-Wen
Single-virus tracking (SVT) offers the opportunity to monitor the journey of individual viruses in real time and to explore the interactions between viral and cellular structures in live cells, which can assist in characterizing the complex infection process and revealing the associated dynamic mechanisms. However, the low brightness and poor photostability of conventional fluorescent tags (e.g., organic dyes and fluorescent proteins) greatly limit the development of the SVT technique, and challenges remain in performing multicolor SVT over long periods of time. Owing to the outstanding photostability, high brightness and narrow emission with tunable color range of quantum dots (QDs), QD-based SVT (QSVT) enables us to follow the fate of individual viruses interacting with different cellular structures at the single-virus level for milliseconds to hours, providing more accurate and detailed information regarding viral infection in live cells. So far, the QSVT technique has yielded spectacular achievements in uncovering the mechanisms associated with virus entry, trafficking and egress. Here, we provide a detailed protocol for QSVT implementation using the viruses that we have previously studied systematically as an example. The specific procedures for performing QSVT experiments in live cells are described, including virus preparation, the QD labeling strategies, imaging approaches, image processing and data analysis. The protocol takes 1–2 weeks from the preparation of viruses and cellular specimens to image acquisition, and 1 d for image processing and data analysis.
研究领域:
病毒学
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细胞生物学
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成像技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Yiheng Mao,Ying Chen,Yuan Li,Longda Ma,Xi Wang,Qi Wang,An He,Xi Liu,Tianyi Dong,Weina Gao,Yanfen Xu,Liang Liu,Liang Ren,Qian Liu,Peng Zhou,Ben Hu,Yiwu Zhou,Ruijun Tian,Zheng-Li Shi
As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.
研究领域:
蛋白质组学
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肺科学
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病理学
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病毒学
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分子生物学
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DOI
PubMed
高影响因子
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