ACS Applied Nano Materials
·
2024
·
IF 5.3
Chu-shu Zhu,Siyue Xiong,Chengxuan Wang,Peitao Dong,Xuezhong Wu
Accurate and convenient diagnosis of the influenza virus is of critical importance to prevent the spread of flu infections and guide therapy and treatment. This work reports the fabrication of a sensitive and quantitative surface-enhanced Raman scattering (SERS)-based lateral flow (LF) strip combined with enzymatic recombinase amplification (ERA) for the highly effective detection of the influenza A virus. Gold-shell silica-core nanoraspberries (NRbs) were used in this SERS-LF strip as a SERS substrate. Practical and convenient detection was accomplished by naked-eye visualization, and highly sensitive quantitative detection was accomplished by monitoring the intensity of the distinct Raman peaks associated with the SERS tags. Under optimal conditions, the sensitivity of this ERA-SERS-LF strip for the DNA standard of the IAV matrix gene is 105 copies/mL by naked-eye visualization, and the limit of detection (LOD) was estimated to be 2.63 × 103 copies/mL by SERS detection, lowered by nearly 40 times compared with visual results due to the signal enhancement of the SERS tags. Besides, quantitative detection for the DNA standard of the IAV matrix gene was obtained with a wide linear range (2.63 × 103 copies/mL to 109 copies/mL). Pseudoviruses of IAV and other respiratory viruses could be successfully identified by using the fabricated ERA-SERS-LF strip. Overall, the findings of this study demonstrate the prospects of the use of the ERA-SERS-LF strip as an effective tool for point-of-care testing (POCT) detection of viruses by virtue of its portability, good sensitivity, quantitative detection ability, and outstanding specificity.
研究领域:
医学诊断
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生物传感
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病毒学
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产品关联
DOI
高影响因子
Cell Death Discovery
·
2025
·Vol. 11
·期 1
·1-13
·
IF 7
Wei Cheng,Xu Yitian,Zheng Ying,Hong Lizhe,Lyu Chen,Li Haibo,Cao Bin
The mortality associated with influenza A virus (IAV) infection typically results from excessive immune responses, leading to immunopathological lung damage and compromised pulmonary function. Various immunomodulators are seen beneficial when used in conjunction with direct anti-infection treatment. Leukotriene B4 (LTB4) is a derivative of arachidonic acid (AA) and has been shown to be advantageous for numerous infectious diseases, allergies, and autoimmune disorders. Nonetheless, the function of LTB4 in influenza infection remains unclear. This study demonstrates that LTB4 and its primary receptor BLT1, as opposed to the secondary receptor BLT2, act as a protective immune modulator during influenza infection in bone marrow-derived macrophages and mouse models. Mechanistically, LTB4 promotes K27-linked and K48-linked polyubiquitination of the NLRP3 protein at its K886 and K1023 sites via a cAMP/PKA-dependent pathway, which inhibits NLRP3 inflammasome assembly and thereby diminishes subsequent NLRP3 inflammasome activation. The consequent decline in the release of IL-1β and IL-18 leads to a reduction in inflammation caused by viral infection. Furthermore, the administration of a LTB4 treatment in a fatal IAV infection model can mitigate the excessive NLRP3 inflammasome activation and reduce IAV-induced severe pulmonary damage. These findings illustrate the protective function of LTB4 in fatal IAV infection by mitigating the severe inflammation induced by the virus.
研究领域:
免疫学
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病毒学
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药理学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Xin Yang,Junxian Li,Chunlan Shan,Xuqin Song,Jian Yang,Hao Xu,Deyuan Ou
In the present study, we investigated whether baicalin could reduce the damage caused to RAW264.7 cells following infection with H6N6 avian influenza virus. In addition, we studied the expression of autophagy-related genes. The morphological changes in cells were observed by hematoxylin and eosin (H&E) staining, and the inflammatory factors in the cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to detect the levels of RAW264.7 autophagosomes, and western blotting and immunofluorescence were used to detect the protein expression of autophagy marker LC3. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA transcription levels of autophagy key factors. The results showed that different doses of baicalin significantly reduced the H6N6 virus-induced damage of RAW264.7 cells. The contents of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the cell supernatant significantly decreased. In addition, the protein expression of LC3 and Beclin-1, ATG12, ATG5 the mRNA levels were significantly decreased. This study showed that baicalin can reduce cell damage and affect the H6N6-induced autophagy level of RAW264.7 cells.
研究领域:
病毒学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
EBioMedicine
·
2022
·
IF 11.205
Mengyi Zhang,Yimeng An,Xi Wu,Meina Cai,Xinyu Zhang,Chaoying Yang,Jincheng Tong,Zhimin Cui,Xueli Li,Weijin Huang,Chenyan Zhao,Youchun Wang
Summary Background Influenza A (H3N2) virus (A/H3N2) has complex antigenic evolution, resulting in frequent vaccine strain updates. We aimed to evaluate the protective effect of the vaccine strains on the circulating strains from past ten years and provide a basis for finding a broader and more efficient A/H3N2 vaccine strain. Methods Eighty-four representative circulating A/H3N2 strains were selected from 65,791 deposited sequences in 2011–2020 and pseudotyped viruses were constructed with the VSV vector. We immunized guinea pigs with DNA vaccine containing the A/H3N2 components of the vaccine strains from 2011 to 2021 and tested neutralizing antibody against the pseudotyped viruses. We used a hierarchical clustering method to classify the eighty-four representative strains into different antigenic clusters. We also immunized animals with monovalent vaccine stock of the vaccine strains for the 2020–2021 and 2021–2022 seasons and tested neutralizing antibody against the pseudotyped viruses. Findings The vaccine strains PE/09, VI/11 and TE/12 induced higher levels of neutralizing antibody against representative strains circulating in recommended year and the year immediately prior whereas vaccine strains HK/14, HK/19 and CA/20 induced poor neutralization against all representative strains. The representative strains were divided into five antigenic clusters (AgV), which were not identical to gene clades. The AgV5 strains were most difficult to be protected among the five clusters. Compared with single-dose immunization, three doses of monovalent vaccine stock (HK/19 or CA/20) could induce stronger and broader neutralizing antibodies against strains in each of the antigenic clusters. Interpretation The protective effect of vaccine strains indicated that the accurate selection of A/H3N2 vaccine strains must remain a top priority. By increasing the frequency of immunization, stronger and broader neutralizing antibodies against strains in all antigenic clusters were induced, which provides direction for a new immunization strategy. Funding This work was supported by a grant from National Key R&D Program of China (No. 2021YFC2301700 ).
研究领域:
病毒学
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免疫学
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流行病学
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DOI
PubMed
高影响因子
JOURNAL OF VIROLOGY
·
2021
·Vol. 95
·期 3
·
IF 5.103
Ning Ma,Xingjie Li,Hongyu Jiang,Yulong Dai,Guofeng Xu,Zongde Zhang
Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus, MA01, to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza virus neuraminidase (NA) unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced lipopolysaccharide (LPS)-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza virus neuraminidase modulates CD83 status and contributes to the “cytokine storm,” which may suggest a new approach to curb this immune injury.IMPORTANCE The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon is referred to as the “cytokine storm.” However, the mechanism by which influenza induces the cytokine storm is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interruption of influenza-induced lung damage.
研究领域:
免疫学
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病毒学
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医学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yuqi Yang,Shengjun Bu,Xiaoying Zhang,Qiqing Duan,Heyuan Meng,Zhuo Hao,Xiuxia He,Jiayu Wan
Infectious diseases caused by the influenza virus are the primary global concern. This study aimed to develop an electrochemical biosensor for detecting influenza A H1N1 virus based on duplex-specific nuclease (DSN) and rolling circle amplification (RCA) technologies. A single-stranded DNA (ssDNA) probe, comprising a recognition sequence for a target sequence of influenza virus H1N1-specific RNA sequence and primer sequence for initiating RCA, was designed and synthesized. A specific sequence of target H1N1 RNA triggered cyclical DSN cleavage of the probe. The released primer sequence then initiated RCA to generate detectable ssDNA-labeled multiple biotins. ssDNA was captured by streptavidin (SA) on the electrode surface and labeled with free Streptavidin-Horseradish Peroxidase (SA-HRP). The H1N1 influenza virus was quantitatively analyzed based on the changing current signal generated on the electrode surface. A linear range from 10 pM to 100 nM and a limit of detection of 0.44 pM were recorded. In addition, the biosensor demonstrated excellent selectivity, repeatability, and stability for analyzing H1N1 in real samples. This biosensor could be applied for the clinical diagnosis of influenza A H1N1 virus.
研究领域:
医学诊断
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分子生物学
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生物传感技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Jiawang Huang,Jianing Shi,Jingmin Fu,Zhuolin Liu,Zhiying Feng,Kangyu Wang,Chunjing Chen,Yi Ning,Fangguo Lu,Ling Li
Ethnopharmacology relevance Maxing Shigan Decoction (MXSGD), derived from the traditional Chinese medicine (TCM) classic Shang Han Lun , is recognized as an effective TCM herbal formula for treating respiratory diseases, although its precise molecular mechanisms against influenza A virus (IAV) have not yet been fully elucidated. Aim of the study This study aimed to clarify the pharmacological effects of MXSGD on IAV-infected pneumonia mouse models, with a particular focus on its regulatory mechanism through miR-1260. Materials and methods The chemical composition of MXSGD was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After establishing IAV-infected mouse models, the pathological changes in lung tissues were observed by hematoxylin-eosin (HE) staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expression levels of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. A co-culture system of MLE-12 and RAW246.7 cells was constructed as the research model. Then, the intracellular miR-1260 expression was detected by RT-qPCR, and the Sema3A expression was examined by immunofluorescence. The macrophages were further transfected with miR-1260 mimic, inhibitor, and Sema3A siRNA to determine whether MXSGD exerts its therapeutic effects through the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway. Subsequently, alveolar macrophage-depleted mouse models were established using CL2MBP, and were infected with IAV. To clarify the role of macrophages in the therapeutic mechanism of MXSGD against IAV, the body weight and organ indices of mice were monitored and recorded; the total protein content and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were measured; the histopathological changes were observed by HE staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expressions of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. Results MXSGD was found to alleviate IAV-induced pathological injury and suppress macrophage recruitment in mouse lung tissues, while downregulating the viral load and levels of inflammatory factors. The attenuation of macrophage recruitment was closely associated with pulmonary epithelial cells, potentially mediated through the miR-1260-targeted Sema3A-regulated PI3K/AKT/mTOR signaling pathway. In cellular experiments, both cell types in the co-culture system were restored following MXSGD treatment, accompanied by lowered intracellular viral load and levels of inflammatory factors. Additionally, macrophage apoptosis and miR-1260 expression were significantly reduced, whereas the Sema3A fluorescence intensity in macrophages was markedly increased. By transfecting miR-1260 mimic, inhibitor, and Sema3A siRNA into co-cultured macrophages, the therapeutic effects of MXSGD were further confirmed to be associated with the miR-1260/Sema3A-mediated PI3K/AKT/mTOR pathway. In IAV-infected models established after pulmonary macrophage depletion, the therapeutic efficacy of MXSGD was partially weakened following elimination of alveolar macrophages. In general, above in vivo findings are consistent with the cellular experimental results, collectively supporting the involvement of the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway in the therapeutic mechanism of MXSGD. Conclusions MXSGD was demonstrated to regulate the PI3K/AKT/mTOR pathway through the macrophage miR-1260/Sema3A axis, through which excessive inflammatory responses in IAV-induced pneumonia were effectively suppressed. The findings provide a novel therapeutic target for antiviral treatment in TCM.
研究领域:
免疫学
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病毒学
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分子生物学
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呼吸病学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Microbiology
·
2025
·
IF 19.4
Jin Shouheng,He Xing,Wang Zheyu,Zhou Tao,Wang Jun,Pan Guihong,Zhang Yin,Ma Ling,Yang Shuai,Wang Liqiu,Wu Yaoxing,Zou Yilin,Qi Nan,Cui Jun
Metabolic pathways determine cellular fate and function; however, the exact roles of metabolites in host defence against influenza virus remain undefined. Here we employed pharmacological inhibition and metabolomics analysis to show that the metabolic pathways of oxaloacetate (OAA) are integrated with antiviral responses to influenza virus. Cytosolic malate dehydrogenase 1 senses intracellular OAA to undergo dimerization and functions as a scaffold to recruit the transcription factor ETS2 for phosphorylation by the kinase TAOK1 at serine 313. The phosphorylated ETS2 translocates into the nucleus and supports optimal expression of TBK1, an indispensable activator of type I interferon responses. OAA supplementation provides a broad-spectrum antiviral ability, and OAA deficiency caused by Acly genetic ablation decreases antiviral immunity and renders mice more susceptible to lethal H1N1 virus infection. Our results uncover a signalling pathway through cellular OAA sensing that links metabolism and innate immunity to coordinate defence against viral challenge.
研究领域:
免疫学
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病毒学
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代谢生物学
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分子生物学
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信号转导
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感染与免疫
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2015
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IF 8.557
Sulong Xiao,Longlong Si,Zhenyu Tian,Pingxuan Jiao,Zibo Fan,Kun Meng,Xiaoshu Zhou,Han Wang,Renyang Xu,Xu Han,Ge Fu,Yongmin Zhang,Lihe Zhang,Demin Zhou
Multivalent effect plays an important role in biological processes , particularly in the specific recognition of virus with its host cell during the first step of infection. Here we report the synthesis of multivalent pentacyclic triterpene grafted on cyclodextrin core and potency of against influenza entry activity. Nine star-shaped compounds containing six, seven and eight pentacyclic triterpene pharmacophore on cyclodextrin scaffold were prepared by way of copper-catalyzed azide-alkyl cycloaddition reaction under microwave activation. Some of the multimers exhibited much potent antiviral activity against H1N1 virus (A/WSN/33), even equivalent or superior to oseltamivir . The most active compound 31 , a heptavalent oleanolic acid- β -cyclodextrin conjugate , shows an up to 125-fold potency enhancement by its IC 50 value over the corresponding monovalent conjugate and oleanolic acid, disclosing a clear multivalent effect. Further studies show that three compounds 31 – 33 exhibited broad spectrum inhibitory activity against other two human influenza A/JX/312 (H3N2) and A/HN/1222 (H3N2) viruses with the IC 50 values at 2.47–14.90 μ M. Most importantly, we found that compound 31, one of the best representative conjugate, binds tightly to the viral envelope hemagglutinin with a dissociation constant of K D = 2.08 μ M, disrupting the interaction of hemagglutinin with the sialic acid receptor and thus the attachment of viruses to host cells. Our study might establish a strategy for the design of new pharmaceutical agents based on multivalency so as to block influenza virus entry into host cells.
研究领域:
药理学
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病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 18
·2000771
·
IF 15.84
Tao Qin,Shang Ma,Xinyu Miao,Yan Tang,Dandan Huangfu,Jinyuan Wang,Jing Jiang,Nuo Xu,Yuncong Yin,Sujuan Chen,Xiufan Liu,Yinyan Yin,Daxin Peng,Lizeng Gao
Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)-based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS-IONzyme increases antigen adhesion to nasal mucosa by 30-fold compared to H1N1 WIV alone. Next, CS-IONzyme facilitates H1N1 WIV to enhance CCL20-driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll-like receptor(TLR) 2/4-dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)-like activity by CS modification catalyzes a reactive oxygen species (ROS)-dependent DC maturation, which further enhances the migration of H1N1 WIV-loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS-IONzyme-based nasal vaccine triggers an 8.9-fold increase of IgA-mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.
研究领域:
免疫学
·
病毒学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Xuhui Huang,Yatian Zhang,Jingwei Chen,Zhijin Yang,Mengya Chen,Zhiwei Xue,Lizan Zhou,Zhaofeng Huang,Yule Zhang,Lulu Zheng,Dawei Zhang
Acute respiratory syndrome coronavirus (SARS-CoV-2), influenza A virus (Flu A), and influenza B virus (Flu B) are highly contagious pathogens that can cause similar clinical manifestations and often co-infect, posing significant challenges for differential diagnosis and disease management. Early and accurate detection of these viruses is crucial for curbing their respiratory transmission. Therefore, there is an urgent need to develop a reliable, rapid, sensitive, and user-friendly tool for detecting multiple respiratory pathogens. Here, we present a triple-channel immunochromatographic system (TCIS) based on quantum dot fluorescent microspheres (QDFM), which includes immunochromatographic test strips and a detection platform integrated with optical and electronic modules. The TCIS utilizes a smartphone for fluorescence image extraction and filtering algorithms, enabling automatic image denoising and quantitative data analysis. Combined with high quantum yield luminescent materials, the system significantly enhances detection sensitivity. The limits of detection (LODs) for Flu B nucleoprotein, Flu A nucleoprotein, and SARS-CoV-2 N protein were as low as 0.301 ng/mL, 0.227 ng/mL, and 0.348 ng/mL, respectively. To evaluate its clinical performance, we tested saliva samples from 15 Flu A patients and 20 healthy controls, demonstrating a sensitivity of 100% and a specificity of 95.2%. This work highlights the potential of TCIS as an efficient, accessible, and accurate home-based diagnostic tool, offering a promising solution for early diagnosis.
研究领域:
生物医学工程
·
病毒学
·
诊断技术
·
即时检测
·
生物分析方法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2015
·Vol. 140
·期 12
·3989-3995
·
IF 4.107
Yuanjian Liu,Linqun Zhang,Wei Wei,Hongyu Zhao,Zhenxian Zhou,Yuanjian Zhang,Songqin Liu
Early and accurate diagnosis is considered the key issue to prevent the further spread of viruses and facilitate influenza therapy. Herein, we report a colorimetric immunosensor for influenza A virus (IAV) based on gold nanoparticles (AuNPs) modified with monoclonal anti-hemagglutinin antibody (mAb). The immunosensor allows for a fast, simple, and selective detection of IAV. In this assay, influenza-specific antibodies are conjugated to AuNPs to create mAb–AuNP probes. Since IAV has multiple recognition sites for probes on the surface, the mAb–AuNP probes can be specifically arranged on the virus surface due to their very specific antigen recognition. In this case, this aggregation of the mAb–AuNP probes produces a red shift in the absorption spectrum due to plasmon coupling between adjacent AuNPs, and it can be detected with the naked eye as a color change from red to purple and quantified with the absorption spectral measurements. The aggregate formation is also confirmed with transmission electron microscopy (TEM) imaging and dynamic light scattering (DLS). Under the optimal conditions, the present immunoassay can sensitively measure H3N2 IAV (A/Brisbane/10/2007) with a detection limit of 7.8 hemagglutination units (HAU). This proposed immunosensor revealed high specificity, accuracy, and good stability. Notably, it is a single-step detection using AuNP probes and UV-vis spectrophotometer for readout, and no additional amplification, e.g., enzymatic, is needed to read the result. This assay depends on an ordered AuNP structure covering the virus surface and can be applied to any virus pathogen by incorporating the appropriate pathogen-specific antibody.
研究领域:
病毒学
·
纳米生物学
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医学诊断
✓ 已验证
DOI
PubMed
高影响因子
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