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JOURNAL OF VIROLOGICAL METHODS · 2014 · IF 1.883

Prophylaxis and therapy of pandemic H1N1 virus infection using egg yolk antibody

Yuan-e Yang,Junlin Wen,Suqing Zhao,Kun Zhang,Yingliang Zhou

Influenza A virus infects the human respiratory system and causes acute and fatal pulmonary diseases. The emergence of drug-resistant viral strains highlights the need for alternative therapeutic approaches. In this work, IgY antibody was raised in immunized laying hens, and its antiviral activity was evaluated in the context of passive immunization. With inactivated whole H1N1 virus, high-titer IgY antibody 9.18   mg/mL egg yolk was induced by the eighth week after immunization. Western blotting and the hemagglutination inhibition (HI) test demonstrated that the IgY antibody could specifically bind the neuraminidase and hemagglutinin of the H1N1 virus. In the plaque reduction assay, the IgY antibody reduced the H1N1 viral infection in MDCK (Madin-Darby canine kidney) cells. In a mouse model, the anti-H1N1 IgY antibody exhibited in vivo protection by reducing the infectious titer of the virus in the lung while maintaining the weight and normal structure of the lung tissue. Additionally, the anti-H1N1 IgY antibody exhibited protective activity comparable to the neuraminidase inhibitor oseltamivir. These results demonstrated that IgY can be easily produced and can offers an effective alternative approach for influenza control.

CAS / MDL: 7411-49-6
研究领域: 免疫学 · 病毒学 · 医学
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Science Advances · 2023 ·Vol. 9 ·期 23 · IF 13.6

Airborne fine particles drive H1N1 viruses deep into the lower respiratory tract and distant organs

Zheng Dong,Juan Ma,Jiahuang Qiu,Quanzhong Ren,Qing’e Shan,Xuefeng Duan,Guangle Li,Yi Y. Zuo,Yu Qi,Yajun Liu,Guoliang Liu,Iseult Lynch,Min Fang,Sijin Liu

Mounting data suggest that environmental pollution due to airborne fine particles (AFPs) increases the occurrence and severity of respiratory virus infection in humans. However, it is unclear whether and how interactions with AFPs alter viral infection and distribution. We report synergetic effects between various AFPs and the H1N1 virus, regulated by physicochemical properties of the AFPs. Unlike infection caused by virus alone, AFPs facilitated the internalization of virus through a receptor-independent pathway. Moreover, AFPs promoted the budding and dispersal of progeny virions, likely mediated by lipid rafts in the host plasma membrane. Infected animal models demonstrated that AFPs favored penetration of the H1N1 virus into the distal lung, and its translocation into extrapulmonary organs including the liver, spleen, and kidney, thus causing severe local and systemic disorders. Our findings revealed a key role of AFPs in driving viral infection throughout the respiratory tract and beyond. These insights entail stronger air quality management and air pollution reduction policies.

CAS / MDL: 22144-77-0
研究领域: 环境科学 · 病毒学 · 公共卫生 · 呼吸医学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2023 · IF 3.4

Therapeutic effects on H1N1-induced pneumonia in mice and intestinal bacteria biotransformation of four main flavonoids from Houttuynia cordata Thunb.

Jiayue Tang,Lishuang Zhou,Guoqi Yuan,Yang Liu,Xunlong Shi,Yan Lu,Daofeng Chen

Flavonoids widely exist in a large number of Chinese herbal medicines with antiviral and anti-inflammatory properties. Houttuynia cordata Thunb. is a traditional Chinese herbal medicine for heat-clearing and detoxification. In our previous research, total flavonoids from H. cordata (HCTF) effectively alleviated H1N1-induced acute lung injury (ALI) in mice. In this study, 8 flavonoids were recognized from HCTF (containing 63.06 % ± 0.26 % of total flavonoids, as quercitrin equivalents) by UPLC-LTQ-MS/MS. Four main flavonoid glycosides in HCTF (rutin, hyperoside , isoquercitrin and quercitrin) and their common aglycone quercetin (100 mg/kg) all showed therapeutic effects on H1N1-induced ALI in mice. The two flavonoids (hyperoside and quercitrin) with higher contents and quercetin showed stronger therapeutic effects on H1N1-induced ALI in mice. Hyperoside, quercitrin and quercetin significantly reduced the levels of pro-inflammatory factors, chemokines , or neuraminidase activity compared with the same dose of HCTF ( p  < 0.05). The results of mice intestinal bacteria biotransformation in vitro showed that quercetin was the main metabolite. The conversion rates of hyperoside and quercitrin were significantly higher by the intestinal bacteria under the pathological state (0.81 ± 0.02 and 0.91 ± 0.01, respectively) than normal state (0.18 ± 0.01 and 0.18 ± 0.12, respectively, p  < 0.001). Our findings showed that hyperoside and quercitrin were the main efficacious components of HCTF for treating H1N1-induced ALI in mice and could be metabolized to quercetin by intestinal bacteria in pathological state to exert their effects.

CAS / MDL: 64-18-6
研究领域: 中药学 · 免疫学 · 微生物学
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ANALYTICAL LETTERS · 2022 · IF 2.267

Ratiometric Fluorescence Determination of Avian Influenza a Virus Subtype H1N1 DNA with Functionalized Quantum Dots and Gold Nanoparticles

Wenmin Ke,Qizhen Lai,Yixia Yang,Jingjing Qian,Xinghu Ji,Zhike He

A new type of ratiometric fluorescence sensor based on DNA functionalized quantum dots (DNA-QDs) and gold nanoparticles (AuNPs) was constructed for sensitive fluorescence determination of the avian influenza A virus subtype H1N1 DNA. Using the nucleic acid strand displacement reaction, the carboxyfluorescein-DNA (FAM-DNA) replaced DNA-QDs on the surface of DNA-AuNPs, so that the fluorescence of QDs increased and the fluorescence of FAM decreased. In the presence of H1N1 DNA, the ends of the DNA on the AuNPs-DNA-QDs conjugates were blocked, preventing strand displacement. The fluorescence intensity ratio of FAM to QDs (F520/F624) was proportional to the concentration of H1N1 DNA. The linear range was from 2.5 to 20.0 nM with a limit of detection of 0.52 nM. Furthermore, this sensor showed good selectivity. This strategy is a simple, accurate, and sensitive tool to detect DNA biomarkers.

CAS / MDL: 1633-78-9
研究领域: 生物化学 · 分子生物学 · 纳米生物学
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Analytical Methods · 2024 · IF 2.7

Label-free H1N1 influenza virus immunosensor based on N-LIG/Au laser induced graphene microelectrode

Yuchen Zhou,Wanchun Chen,Guangyuan Wang,Zhenfeng Lei,Mei Zhang,Yanxia Li

A label-free immunosensor based on N-doped laser direct graphene (N-LIG)/Au electrode was proposed for H1N1 influenza virus detection. By utilizing the instantaneous high temperature of laser irradiation, N atoms generated by the decomposition of melamine dripped onto the surface of LIG electrode to obtain N-LIG with higher conductivity. The doping of N atoms provides a large number of active sites for LIG microelectrodes. Combined with the electrodeposition of Au NPs, and covalently crosslinking antibodies, a simple, highly sensitive and stable immunosensing interface is constructed. The proposed H1N1 influenza virus immunosensor has a detection range of 0.01 fg mL-1 to 10 ng mL-1 with a detection limit as low as 0.004 fg mL-1. The constructed sensor has ultra-high sensitivity, good selectivity, and can be used for complex biological sample analysis, with potential application prospects in preventing the large-scale spread of influenza. Taking advantage of N-LIG electrode’s properties will provide opportunities for developing portable electrochemical biosensors for health and environmental applications.

研究领域: 生物传感器 · 电化学 · 病毒学 · 分析化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Preparation and characterization of curdlan-chitosan conjugate nanoparticles as mucosal adjuvants for intranasal influenza H1N1 subunit vaccine

Honglei Jiang,Shu Zhang,Yipan Chen,Fengshan Wang,Wenjie Jiang

Intranasal vaccination offers crucial protection against influenza virus pandemics. However, antigens, especially subunit antigens, often fail to induce effective immune responses without the help of immune adjuvants. Our research has demonstrated that a polyelectrolyte complex, composed of curdlan sulfate/ O -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/ O -HTCC), effectively triggers both mucosal and systemic immune responses when administrated intranasal. In this study, stable nanoparticles formed by curdlan- O -HTCC conjugate (C O NP) were prepared and characterized. Furthermore, the efficacy of C O NP was evaluated as a mucosal adjuvant in an intranasal influenza H1N1 subunit vaccine. The results revealed that C O NP exhibits uniform and spherical morphology, with a size of 190.53 ± 4.22 nm, and notably, it remains stable in PBS at 4 °C for up to 6 weeks. Biological evaluation demonstrated that C O NP stimulates the activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), both in vitro and in vivo . Furthermore, intranasal administration of C O NP effectively elicits cellular and humoral immune responses, notably enhancing mucosal immunity. Thus, C O NP emerges as a promising mucosal adjuvant for influenza subunit vaccines.

研究领域: 药剂学 · 免疫学 · 疫苗学 · 纳米技术 · 生物医学工程
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2022 · IF 3.571

Exploring the anticomplement components from Fagopyrum dibotrys for the treatment of H1N1-induced acute lung injury by UPLC-Triple-TOF-MS/MS

Xiaojiang Wang,Yukun Jiao,Haiyan Zhu,Yan Lu,Daofeng Chen

In the present study, a procyanidins-enriched fraction (PCE) from the rhizome of Fagopyrum dibotrys was obtained by anticomplement activity-guided fractionation. PCE could alleviate H1N1-induced ALI in mice by reducing weight loss, decreasing lung index, and regulating cytokine levels in lung tissue. PCE contained 76.5 ± 1.1% procyanidins with a mean degree of polymerization (mDP) of 5.24 ± 0.16. Meanwhile, thirty-three chemical constituents, including 27 procyanidins and 6 other compounds, were recognized by UPLC-Triple-TOF-MS/MS. Among them, twenty recognized procyanidins were composed of (epi)catechin with B-type link, while the rest consisted of (epi)catechin gallate . Furthermore, six compounds were obtained by preparative HPLC on a C 18 column (250 × 10.0 mm, 5 µm), and their structures were confirmed by mass spectrum (MS), nuclear magnetic resonance (NMR), and specific rotation. The structure-activity relationship analysis indicated that DP and galloylation were closely related to the anticomplement activity of procyanidins. The obtained results revealed that anticomplement procyanidins were one kind of the potentially effective materials of F. dibotrys against H1N1 influenza virus infection, and the in vivo efficacy of these compounds was worthy of further investigation.

CAS / MDL: 196618-13-0
研究领域: 药理学 · 病毒学 · 分析化学 · 免疫学
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Frontiers in Pharmacology · 2019 · IF 3.845

Epigoitrin, an Alkaloid From Isatis indigotica, Reduces H1N1 Infection in Stress-Induced Susceptible Model in vivo and in vitro

Luo Zhuo,Liu Li-Fang,Wang Xiao-Hua,Li Wen,Jie Chong,Chen Huan,Wei Fan-Qin,Lu Dan-Hua,Yan Chang-Yu,Liu Bo,Kurihara Hiroshi,Li Yi-Fang,He Rong-Rong

Stress has been proven to modulate an individual’s immune system through the release of pituitary and adrenal hormones such as the catecholamines, growth hormone, and glucocorticoids. These signal molecules can significantly alter the host immune system and make it susceptible to viral infection. In this study, we investigate whether epigoitrin, a natural alkaloid from Isatis indigotica, provides protection against influenza infection by reducing the host’s susceptibility to influenza virus under stress and its underlying mechanism. To support it, the mouse restraint stress model and the corticosterone-induced stress model were employed. Our results demonstrated that epigoitrin significantly decreased the susceptibility of restraint mice to influenza virus, evidenced by lowered mortality, attenuated inflammation, and decreased viral replications in lungs. Further results revealed that epigoitrin reduced the protein expression of mitofusin-2 (MFN2), which elevated mitochondria antiviral signaling (MAVS) protein expression and subsequently increased the production of IFN-β and interferon inducible transmembrane 3 (IFITM3), thereby helping to fight viral infections. In conclusion, our study indicated that epigoitrin could reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.

CAS / MDL: 1072-93-1
研究领域: 免疫学 · 病毒学 · 药理学
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Virulence · 2024 · IF 5.5

Immunosuppressants exert antiviral effects against influenza A(H1N1)pdm09 virus via inhibition on nucleic acid synthesis, mRNA splicing and protein stability

Xin Wang,Feiyang Pu,Xuanye Yang,Xili Feng,Jiayou Zhang,Kai Duan,Xuanxuan Nian,Zhongren Ma,Xiao-Xia Ma,Xiao-Ming Yang

Influenza A virus (IAV) poses threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of ten immunosuppressants, explored the antiviral mechanisms of immunosuppressants and demonstrated the combination effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibited viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibited IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG and filgotinib could be the preferential choices for patients who must take immunosuppressants but at risk of influenza virus infection.

研究领域: 药理学 · 病毒学 · 免疫学
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NEW JOURNAL OF CHEMISTRY · 2022 ·Vol. 47 ·期 4 ·1685-1690 · IF 3.925

Ultrasensitive electrochemical immunoassay for screening the influenza A (H1N1) virus based on atomically Ru-dispersed nitrogen-doped carbon

Jiancheng Lin,Jingjing Liu,Jin Xu

Herein, a versatile electrochemical immunoassay was designed based on an atomically Ru-dispersed nitrogen-doped carbon (Ru–CN) modified disposable screen-printed carbon electrode (SPCE) for sensitive and specific screening of low-abundance influenza A (H1N1) virus with an innovative split-type strategy. Atomic-level Ru–CN can be obtained after pyrolysis of an acetylacetone ruthenium-encapsulated metal–organic framework (zeolite imidazolate framework 8, ZIF-8), which shows a good electrochemical response to ascorbic acid. To achieve H1N1 detection, an alkaline phosphatase (ALP)-loaded sandwich immunoassay was used to generate ascorbic acid in a 96-well plate, which is then dropped onto the Ru–CN modified disposable SPCE to generate a significant current signal using differential pulse voltammetry (DPV). Under optimal conditions, the DPV peak currents were positively correlated with the H1N1 influenza virus concentration in the dynamic working range of 1.0 ng mL−1 to 10 000 ng mL−1 with a limit of detection (LOD) of 0.28 ng mL−1. During the detection of the H1N1 influenza virus, we also focused on the analysis performance of the sensor system and found that the platform has good reproducibility, high specificity, and acceptable stability. Impressively, the proposed sensing system is equivalent to the commercial detection method (ELISA) in the measurement of the H1N1 influenza virus from clinical samples, which further confirms the accuracy of the Ru–CN-based electrochemical immunoassay method. This enhanced analytical performance through atomic-level dispersed metals gives a new horizon to develop highly sensitive electrochemical immunoassays in the field of early detection of epidemic viruses.

研究领域: 分析化学 · 电化学 · 病毒学 · 生物传感器 · 医学诊断
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Fluorescence/Colorimetric Lateral Flow Immunoassay Based on Dual-Aptamer Domain Recognition and Upconversion Signal Amplification for Sensitive H1N1 Hemagglutinin Detection

Zhen Wan,Haijiang Gong,Qi Liu,Qingyu Wang,Ping'an Ma,Fei He,Qingqing Wang,He Ding,Shili Gai,Piaoping Yang

Rapid and specific detection of influenza A viruses is critical for pandemic response. However, traditional lateral flow immunoassays (LFIAs) face challenges in sensitivity, signal reliability, and cross-reactivity. Herein, a dual-aptamer-functionalized lateral flow platform is designed, integrating upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) to mitigate these bottlenecks through a synergistic mechanism: near-infrared-excited luminescence resonance energy transfer (LRET) for fluorescence modulation, dual-aptamer domain recognition for specific binding, and fluorescence-colorimetric dual readouts for orthogonal validation. Specifically, LRET serves as the core signal transduction mechanism, with aptamer1-conjugated UCNPs as donors and aptamer2-conjugated AuNPs as acceptors, regulated by target-induced proximity. Dual-aptamers recognizing distinct hemagglutinin (HA) epitopes enhance specificity, minimizing cross-reactivity with non-target subtypes (H5N1, H6N1, etc.) while ensuring high-affinity H1N1 HA binding. Such synergy enables significant signal amplification, achieving a fluorescent limit of detection (LOD) of 2.814 ng mL −1 (2.84–5.33-fold better than traditional AuNP-LFIAs) with a linear range of 4–10 ng mL −1 . Importantly, the dual-mode design integrates upconversion fluorescence and AuNPs colorimetry, mitigating variability, ensuring precision, and enabling 20-minute qualitative detection (up to 100 ng mL −1 ) for point-of-care testing (POCT). Thus, this work presents a scalable POCT paradigm via apt-LRET integration, leveraging dual-aptamer recognition and LRET-mediated amplification for on-site viral diagnostics with pandemic-response timeliness.

研究领域: 病毒学 · 生物传感器 · 即时检测 · 纳米生物技术 · 诊断成像
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Acta Pharmaceutica Sinica B · 2025 · IF 14.6

An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation

Xinxing Li,Wenxin Ding,Yan Lu,Haiyan Zhu,Weilian Bao,Yang Liu,Jiaren Lyu,Lishuang Zhou,Hong Li,Jiyang Li,Daofeng Chen

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD 50 ) and methicillin-resistant Staphylococcus aureus (MRSA, 10 7 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

研究领域: 免疫学 · 微生物学 · 药理学 · 呼吸医学
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