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  • 简介:AbstractAvian influenza remains a threat to human wellbeing. Hypochlorite derivatives are commonly used as disinfectants to prevent the spread of the disease. The World Health Organization (WHO) has listed chlorine dioxide (ClO2) as an A1-level, safe, and efficient disinfectant. In this study, we tested the efficacy of ClO2, in aqueous solution and gas forms, against avian influenza A (H7N9) virus. The virus suspension was mixed with ClO2 aqueous solutions of various concentrations and for various time intervals. Aliquots of the mixture were then serially diluted, and the 50% tissue culture infective dose (TCID50) was measured with a hemagglutination test on MDCK cells. ClO2 gas produced from generators was introduced in a chamber containing the virus suspension in a Petri dish. The infective activity of the surviving virus was measured by the hemagglutination test. An aqueous solution of ClO2 at 126 µg/mL for 15 s was effective given that no surviving virus was detected with the hemagglutination test. ClO2 gas at >5 µL/L sustained for 1 h inactivated the virus effectively, while at 2.5 µL/L for 1 h, it only partially inactivated the virus. ClO2 as gas or aqueous solution at a certain concentration is effective in inactivating the H7N9 virus, and can be applied for the decontamination and disinfection of environments.

  • 标签: Chlorine dioxide Influenza virus A H7N9 Disinfection Aqueous solution Gas ClO2
  • 简介:AbstractBackground:The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

  • 标签: Avian influenza H7N9 Monoclonal antibody Neutralizing activity
  • 简介:AbstractBird infections with highly pathogenic avian influenza A(H5N6) viruses have been identified since 2014. With very limited occasion, the virus could sporadically spilled over to infect humans. It has been recognized that all human infections were within southern region of Mainland China until the case reported here in Beijing in Aug. 2019. This was the first human case infected with highly pathogenic avian influenza A(H5N6) virus in northern China. The infection was confirmed by real-time RT-PCR assay. The whole genome sequences were obtained from clinical sample. Genetic characteristics of the virus were identified similar to those of previous avian influenza A(H5N6) viruses, retaining the main features of the avian influenza virus.

  • 标签: Highly pathogenic avian influenza H5N6 Human infection
  • 作者: Fang Qiongqiong Wang Dayan
  • 学科: 医药卫生 >
  • 创建时间:2020-08-10
  • 出处:《生物安全与健康 (英文)》 2020年第02期
  • 机构:National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; WHO Collaborating Center for Reference and Research on Influenza, Beijing 102206, China; Key Laboratory for Medical Virology, National Health Commission, Beijing 102206, China
  • 简介:AbstractAnti-influenza drugs are one of the most critical pathways for control of influenza virus infection. Drugs that have been developed or are developing may function via different mechanisms, and so far, inhibitors of influenza virus polymerase are among the most promising types of drugs. Favipiravir and Baloxavir, also named T-705 and Xofluza respectively, have been approved for influenza treatment in Japan and the United States. Favipiravir effectively and selectively inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses while Baloxavir specifically targets the cap-dependent endonuclease PA of influenza viruses. These two drugs have been suggested as the first candidate drugs for influenza infection treatment, especially for strains resistant to other anti-influenza drugs. This review will focus on the pharmaceutical mechanisms and anti-influenza activity of these two drugs.

  • 标签: Favipiravir Baloxavir Influenza virus Anti-influenza drug Drug target
  • 简介:AbstractViral isolation in cell cultures has been regarded for decades as the "gold standard" for the laboratory diagnosis of influenza viral infections. Not all viral strains could be isolated from clinical samples. This study aimed to quantify the viral load in the samples before isolation to save working time and improve working efficiency. Four hundred samples from patients with influenza-like cases were confirmed pdmH1N1 positive (200 cases) and B Victoria (BV) positive (200 cases) by whole-genome sequencing and analyzed by ddPCR for viral load in samples before isolation, and isolation results were verified by hemagglutination (HA) assay and hemagglutination-inhibition (HI) tests. Probit regression analysis was used to calculate the isolation viral load limit with a 95% probability level by SPSS 19.0 software. The results showed that the isolation limit of viral load was 4.9 × 104 (95% CI: 2.5 × 104-9.0 × 104) copies/mL for pdmH1N1 and 1.9 × 104 (95% CI: 7.8 × 103-3.6 × 104) copies/mL for BV. The isolation rate of clinical samples is positively correlated with the viral load in clinical samples, which can be used for viral culture, providing important guidance for daily work.

  • 标签: Influenza virus ddRT-PCR Viral load Viral isolation
  • 简介:InordertorevealvariationandrevolutionofNPgenesofhumanavianH_5N_1influenzavirusstrains,theNPgeneofahumanavianH_5N_1influenzavirusstraininGuangdongwassequencedandtheglobalNPgenesofstrainswereretrieved.ThesequenceswereanalyzedbyDNAStar5.0,andtheevolu-tionaryspeedwasstudiedwithreferencetotheepidemiologicaldata.ItwasfoundthatNPgenesof45strainsduring1997-2006werehomologicallyclassifiedintothreegroups:strainsin1997-1998,strainsin2004-2005andstrainsfrom2003to2006.Therewere35substitutionsinNPsinallstrainsaccountingforaratioof7.03%(35/498).Anadditionalglycoproteindomain(NGT_(430-432))wasfoundinNPgenesinthestrainsof2003-2006,themutationofN_(370)SinGD-01-06resultedinoccurrenceofonemoreglyco-proteindomain(NES_(368-370)).Inthesynonymousvariation,K_svaluesinNPwere2.03×10~(-5)-2.55×10~(-5)Nt/dandK_avaluesinNPwere1.58×10(-6)-3.10×10~(-6)Nt/d.Theredidn′texistobviouslyselectivepres-sure.Anadditionalglycoproteindomainineverystrainof2003-2006andonemoreinstrainGD-01-06mightchangetheantigenicityofhumanavianH_6N_1influenzavirus.ThevariationonhumanavianH_5N_1influenzastrainsoccurredfrequentlyinthenaturalworld,whichwouldresultinhighprobabilityofhu-man-humantransmissionalongwiththenaturalevolutionofthevirus.

  • 标签: NP基因 禽流感 H5N1病毒 基因表达
  • 简介:AbstractBackground:The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19.Methods:Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups.Results:Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ2 = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ2 = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir.Conclusions:The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

  • 标签: Influenza A Coronavirus disease 2019 Inflammation biomarker Fatality rate
  • 简介:AbstractWe conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017-2018 and 2018-2019, we collected environmental samples from 14 LPMs, 4 poultry farms, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% - 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology.

  • 标签: Avian influenza virus Environmental surveillance Live-poultry-market
  • 简介:AbstractInfluenza A (H3N2) virus has a faster evolution rate than other types of influenza viruses. In this study, whole genome sequencing was performed to better understand the molecular evolution of influenza H3N2 and the protective effect of influenza virus vaccine in Qinghai Province, China, in 2017. Complete sequences of eight gene segments of two seasonal influenza H3N2 isolates were sequenced and analyzed using DNASTAR and MEGA 6.06 software. Additionally, the three-dimensional structure of the HA protein was predicted using the SWISS-MODEL server. Phylogenetic and amino acid sequence analysis revealed that two Qinghai H3N2 isolates were typical low-pathogenic influenza viruses, and were relatively closely related to the 2016-2017 vaccine strain, 3C.2a-A/Hong Kong/4801/2014. The presence of several antigenic site substitutions (T131K, G/R142K, K160T and R261Q in the HA protein) were specific for the two Qinghai H3N2 virus strains. In addition, amino acid substitution of K160T at the glycosylation site of HA and H75P in PB1-F2 in Qinghai isolates might affect the antibody binding ability and virulence of the influenza virus. The presence of several antigenic site mutations in the Qinghai H3N2 isolates confirmed the evolution of circulating H3N2 strains.

  • 标签: Influenza virus Subtype H3N2 Influenza virus vaccines Whole genome sequencing
  • 作者: Xu Zhi-Wei Li Zhong-Jie Hu Wen-Biao
  • 学科: 医药卫生 >
  • 创建时间:2020-08-10
  • 出处:《贫困所致传染病(英文)》 2020年第01期
  • 机构:School of Public Health and Social Work & Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; School of Public Health, Faculty of Medicine, University of Queensland, Brisbane, Australia,Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China,School of Public Health and Social Work & Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • 简介:AbstractBackground:Understanding the global spatiotemporal pattern of seasonal influenza is essential for influenza control and prevention. Available data on the updated global spatiotemporal pattern of seasonal influenza are scarce. This study aimed to assess the spatiotemporal pattern of seasonal influenza after the 2009 influenza pandemic.Methods:Weekly influenza surveillance data in 86 countries from 2010 to 2017 were obtained from FluNet. First, the proportion of influenza A in total influenza viruses (PA) was calculated. Second, weekly numbers of influenza positive virus (A and B) were divided by the total number of samples processed to get weekly positive rates of influenza A (RWA) and influenza B (RWB). Third, the average positive rates of influenza A (RA) and influenza B (RB) for each country were calculated by averaging RWA, and RWB of 52 weeks. A Kruskal-Wallis test was conducted to examine if the year-to-year change in PA in all countries were significant, and a universal kriging method with linear semivariogram model was used to extrapolate RA and RB in all countries.Results:PA ranged from 0.43 in Zambia to 0.98 in Belarus, and PA in countries with higher income was greater than those countries with lower income. The spatial patterns of high RB were the highest in sub-Saharan Africa, Asia-Pacific region and South America. RWA peaked in early weeks in temperate countries, and the peak of RWB occurred a bit later. There were some temperate countries with non-distinct influenza seasonality (e.g., Mauritius and Maldives) and some tropical/subtropical countries with distinct influenza seasonality (e.g., Chile and South Africa).Conclusions:Influenza seasonality is not predictable in some temperate countries, and it is distinct in Chile, Argentina and South Africa, implying that the optimal timing for influenza vaccination needs to be chosen with caution in these unpredictable countries.

  • 标签: Influenza a Influenza B Seasonality Spatial pattern Vaccination
  • 简介:流行性感冒A病毒(IAV)感染是一个主要全球公共的健康问题。然而,因素在调停包含了煽动性的反应到这感染和他们糟糕理解的关系遗体。这里,我们证明IAV感染刺激可溶的IL-6受体(sIL-6R)的表示,涉及IL-6发信号的多功能的蛋白质。有趣地,sIL-6R表示upregulated它的自己的ligand,支持inflammatorycytokineIL-32的IL-6和那些的层次。调停shRNAsIL-6R击倒压制的IL-6和IL-32,显示这条规定在IAV感染期间依赖于sIL-6R。而且,我们的结果证明IL-32参予禁止sIL-6R的一个否定反馈环当时upregulatingIL-6表示在IAV感染期间。因此,我们证明sIL-6R是涉及对病毒的感染的尖锐煽动性的反应的一个关键细胞的因素。

  • 标签: A型流感病毒 病毒感染 IL-6 RNA介导 细胞因子 炎症反应
  • 简介:AbstractBackground:Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.Methods:Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.Results:MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs.Conclusion:MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

  • 标签: MicroRNA-155 Sphingosine 1-phosphate receptor 1 Influenza A virus Endothelial cells
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  • 简介:严重流行性感冒为人在它的毒力仍然保持不平常。复杂并发症或最终,从这些感染产生的死亡经常与proinflammatorycytokine生产的hyperinduction被联系,它也作为‘被知道;cytokinestorm’;。为这疾病,immunomodulatory治疗可以改进结果,这被建议了,与或没有抗病毒的代理人的联合。这里,我们考察免疫系统的各种各样的受动器怎么开始cytokine暴风雨并且在主人加重病理学的损坏的当前的文学。我们也在严重流行性感冒为cytokine暴风雨的治疗考察一些当前的immunomodulatory策略,包括corticosteroids,peroxisome激活proliferator的受体收缩筋,sphingosine-1-phosphate受体1收缩筋,cyclooxygenase-2禁止者,抗氧化剂,anti-tumour-necrosis因素治疗,静脉内的免疫球蛋白治疗,statins,arbidol,植物,并且另外的潜在的治疗学的策略。

  • 标签: 免疫治疗 细胞因子 风暴 流感 免疫调节 受体激动剂
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  • 作者: Jin Cong Che Bin Guo Zhengyuan Li Chuan Liu Yang Wu Wei Wang Shiwen Li Dexin Cui Zongqiang Liang Mifang
  • 学科: 医药卫生 >
  • 创建时间:2020-08-12
  • 出处:《生物安全与健康 (英文)》 2020年第01期
  • 机构:Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of People's Republic of China, National Institute for Viral Disease Control and Prevention (IVDC), Chinese Center for Disease control and Prevention (China CDC), Beijing 102206, China;National Center for AIDS/STD Control and Prevention, China CDC, Beijing 102206, China,Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of People's Republic of China, National Institute for Viral Disease Control and Prevention (IVDC), Chinese Center for Disease control and Prevention (China CDC), Beijing 102206, China,State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China,Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of People's Republic of China, National Instit
  • 简介:AbstractEbola 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.

  • 标签: Ebola viruses Single particle tracking Lipid raft Cell entry Pathogenesis
  • 简介:Whitespotsyndromevirus(WSSV)isoneofthemajorshrimppathogenscausinglargeeconomiclossestoshrimpfarming.Inanattempttoidentifytheenvelopeproteinsinvolvedinthevirusinfection,purifiedWSSVvirionsweremixedwiththreeantiseraagainstWSSVenvelopeproteins(VP39,VP124andVP187),individually.Andthentheywereinjectedintramuscularlyintocrayfish(Procambarusclarkii)toconductinvivoneutralizationassays.TheresultsshowedthatforgroupsinjectedwithvirionsonlyandgroupsinjectedwiththemixtureofvirionsandantiserumagainstVP124,thecrayfishmortalitieswere100%and60%onthe8thdaypostinfection,individually.ThevirusinfectioncouldbedelayedorneutralizedbyantibodyagainsttheenvelopeproteinVP124.QuantitativePCRwasusedtofurtherinvestigatetheinfluenceofthreeantiseradescribedaboveonthevirusinfection.TheresultsshowedthattheantiserumagainstVP124couldrestrainthepropagationofWSSVincrayfish.AlloftheresultssuggestedthattheviralenvelopeproteinVP124playedaroleinWSSVinfection.

  • 标签: 白斑病毒 蛋白质 抗体 感染
  • 简介:流行性感冒病毒红血球凝聚素的梗区域很好相对与球状的头领域相比被保存,它对流行性感冒用作一支通用疫苗使它成为一个潜在的目标。然而,在红血球凝聚素的CD4T房间的角色梗特定的有免疫力的反应不是清楚的。这里,我们识别了在流行性感冒的尚不致命的感染以后从红血球凝聚素梗领域包含残余HA2113-131的老鼠CD4T房间epitope。响应有识别epitope的刺激,从感染的老鼠导出的splenocytes显示出象degranulation一样由IL-2,TNF-和IFN-生产出现的重要polyfunctionality。而且,与相应于这CD4T房间epitope的肽使免疫的老鼠展出了CD4T房间受体分享的interindividual序列,和他们有更高的幸存率与流行H1N1流行性感冒的致命的剂量跟随挑战病毒。因此,我们的数据表明了红血球凝聚素的一个关键角色在对流行性感冒病毒感染的主机免疫者反应的梗特定的CD4T房间。

  • 标签: BALB/c小鼠 T细胞表位 流感病毒 抗原表位 CD4 血凝素