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Human avian-origin influenza A (H7N9)virus is a novel subtype of avian influenza A virus,which firstly emerged at the end of March 2013 in Shanghai and Anhui province.It rapidly spread in China within a short time,causing high morbidity and mortality,arousing fear and panic in public,and attracting extensive attention worldwide.The analysis of human H7N9 avian influenza virus gene shows a high affinity for α-2,6-linked sialic acid receptors expressed on human respiratory epithelial cells.At present,the sporadic cases of human H7N9 avian influenza virusare occasionally reported with an epidemic peaksat winter and spring.This article reviews clinical features,epidemiology and genetic characteristics of H7N9 avian influenza virus,proving scientific evidences foreffective prevention and control of H7N9 virus infection.
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Objective To predict and identify liner B-cell epitopes in the hemagglutinin ( HA) of human-infected avian-origin H7N9 influenza virus and analyze the specificity of H7 subtype.Methods Three serum samples collected at different times from the same patient who was confirmed to be infected with H7N9 influenza virus were provided by Shaoxing People’s Hospital, and one serum sample from healthy person was collected as the control.The extracellular region of HA protein was predicted by TMHMM Sever v.2.0.The potential B-cell epitopes were predicted by DNAStar Lasergene’ s Protean, BcePred and ABCpred tools, and the immunogenicity of the predicted B cell antigen epitopes was assessed by indirect enzyme-linked immunosordent assay ( ELISA ) .H7 subtype specificity was analyzed by comparing HA protein amino acid sequence with H7N9 and H1-H16 subtype influenza virus from Genbank using Clustal X 2.1 software, and Cn3D 4.3.1 software was used to detect the distribution and 3D structure of predicted epitopes on the HA protein of H7N9.Results The potential B-cell epitopes may be located in 172-183, 363-380, 452-472 and 491-506 of extracellular N-terminus of HA protein.ELISA showed that four predicted eptiopes specifically reacted with positive serums from patient.Multi-sequence alignment demonstrated that peptide 172-183 and 363-380 had higher H7 subtype specificity compared with amino acid sequences of other subtypes.Moreover, the predicted linear B-cell epitopes all located on the surface of HA protein according to the 3D structure analysis.Conclusion Four potential B-cell epitopes were identified, in which peptide 172-183 and 363-380 have higher H7 subtype specificity, and may be used in the design of epitope-based vaccines and diagnostics tests.
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Objective To analyze the molecular characteristics of human pathogenic avian influenza A H7N9 virus.Methods The gene sequences of avian influenza A H7N9 virus (30 human-originated and 15 avian-originated) isolated in Zhejiang province from 2013 to 2015 were downloaded from Global Initiative on Sharing Avian Influenza Data ( GISAID), and then the evolution characteristics, the sites related to receptor binding, virulence and drug resistance of H7N9 virus were analyzed by MEGA 6.0 software. Results There were minor differences in HA and NA genes between human H7N9 virus strains and poultry reference strains in Zhejiang province with the homology of 98.0%-100.0% and 97.4%-100.0%, respectively.Viral amino acid variation showed that 30 representative strains had mutations at 226 (Q226L/I) and 186(G186V) sites in HA protein, and all strains isolated from 2015 had A134V mutation;one strain had R294K mutation in NA gene;19 strains had E627K mutation in PB2 and 2 strains had D701N mutation;mutation S31N was found in M2 gene in all isolates; and all HA cleavage sites were PEIPKGR↓GLF, indicating low pathogenic strain.Conclusions The homology of HA and NA genes is high between poultry reference strains and human H7N9 virus strains in Zhejiang province during 2013 and 2015.Strains have some significant mutations of amino acid in HA and NA protein.All isolates show ion channel inhibitors ( Amantadine) resistance, and some isolates show resistance mutations with neuraminidase inhibitors.
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Objective To examine the clinical features of sporadic patients with H7N9 avian influenzain Taizhou city of Zhejiang province and to characterize its viral genes.Methods Fifteen patients with H7N9 influenza infection confirmed by Zhejiang Provincial Centre for Disease Control and Prevention during January 201 4 and January 201 5 were included in the study.The basic diseases,poultry exposure history,clinical manifestation,laboratory examination,imaging features,treatment and outcome and viral gene sequencing were analyzed retrospectively.Results The first clinical symptoms were fever and cough in all patients,acuterespiratory distress syndrome(ARDS)occurred in 1 3 patients,the average time from onset to antiviral therapy was (7 ±2)d.Among 1 5 patients,9 survived and 6 died,including 2 died of multiple organ failure (MOF).The phylogenetic tree showed that there was highly homologous in hemagglutinin (HA)and neuraminidase(NA)genes between human H7N9 virus strains and poultry reference strains.The result of genetic sequencing indicated that human H7N9 virus strains had mutations at 226 (Q226L)sites in HA protein.Conclusions ARDS is likely to occur in patients with H7N9 viral infection,and early antiviral treatment usually leads to a good prognosis.With the occurrence of adaptive mutation in avian influenza virus H7N9,spread from poultry to the human beings may take place.
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Objective To develop and validate a mortality risk prediction model for patients infected with avian influenza A H 7N9 virus.Methods A stratified and random sampling method was adopted for selection of subjects .A total of 102 patients infected with avian influenza A H7N9 virus, who were admitted to the designated hospitals in Zhejiang Province during March 2013 and March 2015, were enrolled.Standard questionnaires were used to collect data about demographic , epidemiologic and clinical characteristics , and the data were retrospectively reviewed . Univariate analysis and stepwise logistic regression analysis were used to identify the mortality risk factors of patients infected with avian influenza A H7N9 virus, and nomogram was applied to develop the risk prediction model .The accuracy of the prediction model was assessed using Concordance index (C-index) and receiver operating characteristic (ROC) curve. Results Stepwise multiple logistic regression analysis showed that age ≥60 years (χ2 =3.98, OR=2.99, 95%CI:1.05-9.21, P<0.05), increased initial neutrophil count (χ2 =6.66,OR=5.06, 95%CI:1.56-18.83, P<0.05), C-reactive protein≥120mg/L (χ2 =8.63, OR=5.15, 95%CI:1.79-16.31, P<0. 01), poor hand hygiene (χ2 =6.83, OR =10.29, 95%CI:2.18-81.49, P <0.01) and 5 days of incubation period or shorter (χ2 =7.23, OR=4.75, 95%CI:1.59-15.80, P<0.01) were independent risk factors for mortality of patients .Based on the above study , a risk prediction model of nomogram was developed.Poor hand hygiene (grade A, 100.0 points) ranked on the top of all risk factors, followed by C-reactive protein≥120 mg/L (grade B, 76.5 points), increased initial neutrophil count (grade C, 70.5 points), 5 days of incubation period or shorter (grade D, 62.0 points) and age ≥60 years (grade E, 51.0 points).The C-index and the area under the curve were 0.833 and 0.817 for the nomogram model , respectively;and the nomogram model fitted well .Conclusion Nomogram model can effectively predict and estimate the risk of death for patients infected with avian influenza A H 7N9 virus.
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Objective To investigate the risk factors related to mortality in human avian influenza A (H7N9)cases in Hangzhou.Methods The clinical and epidemiological data of 61 H7N9 patients whose diagnoses were confirmed by laboratory tests between 1st March,2013 and 2nd March,2014 in Hangzhou were collected.Descriptive analysis and univariate analysis were used to analyze the demographic,clinical and epidemiological characteristics and treatment outcomes.Patients were classified into improvement group and death group according to treatment outcomes,and risk factors for death were explored.Chi square test and t test were used for statistical analysis.Results A total of 61 patients were included in this study,among which 20(32.8%)patients died.The ratio of men to women for death attributed to H7N9 infection was three to one.The mean age of patients in death group was (63.6 ±3.8)years,which was older than that in improvement group ([55 .4±2.2]years,t =1 .97,P =0.05 ).The univariate analysis showed that the risk factors of mortality included over 60 years (χ2 =5 .16,P =0.02;OR =3.65 ,95 %CI :1 .19-11 .13 ),low education level (χ2 = 5 .42,P =0.02;OR =4.20,95 %CI :1 .24 - 14.00 ), chronic diseases (χ2 =4.67,P =0.03;OR=3.81 ,95 %CI :1 .12-12.69),bad hand hygiene (χ2 =4.05 , P =0.04;OR=4.67,95 %CI :1 .04 -11 .56 ),C-reactive protein (CRP)≥120 mg/L (χ2 =4.04,P =0.04;OR=6.00,95 %CI :1 .04-35 .33),increased initial neutrophil count (χ2 =3.90,P =0.05 ;OR=4.58,95 %CI :1 .01 -34.22)and decreased initial lymphocyte count (χ2 =7.12,P =0.01 ;OR =7.53, 95 %CI :1 .63 - 24.51 ).Conclusion Over 60 years,low education level,chronic diseases,bad hand hygiene,CRP≥ 120 mg/L,increased initial neutrophil count and decreased initial lymphocyte count are identified as risk factors for death in H7N9 cases in Hangzhou.
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The origin,diversity,hemagglutinin protein and mutations of avian influenza A (H7N9) virus are widely studied recently.Although this virus is low-pathogenic in domestic poultry,it becomes highly pathogenic in human when gene mutations occur.The available evidence has revealed that the novel avian influenza A (H7N9) virus is a multiple gene reassortment,and virus shedding in quail and chickens is much higher than in other species.When human infected with H7N9 virus,immune responses will be activated,and massive cytokines and chemokine are produced,which may result in secondary hemophagocytic syndrome and multiple organ dysfunction.The prognosis of H7N9 viral infection may be associated with high level of angiotensin Ⅱ in plasma and the genetic trait of individuals (carrying rs12252-C/C genotype IFITM3).This paper reviews the recent progress on H7N9 virus infection,to provide reference for the control of human infection with H7N9 avian influenza virus and the management of severe cases.
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Objective To conduct a bibliometric analysis of international scientific literatures on research of avian influenza. Methods We performed a search in the Web of Science (WoS) database and analyzed the relevant records with Thomson Data Analyzer (TDA) and citation trees. Results Due to the rapid growth in publications by the United States and China, the number of publications on research of avian influenza has increased remarkably since 2005. The publication of Japan and Netherlands were of high quality due to support of international research programs. The researches about H5N1 virus mutation by the United States, Japan and Netherlands were the typical achievement of the area but also triggered arguments. Conclusion More international efforts arewarranted on research of H7N9 and other influenza viruses.
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Objective To investigate the evolutionary characteristics and important amino acid sites of the neuraminidase (NA) gene of the novel influenza virus A/H7N9 in 2013 epidemic. Methods The NA gene sequences of influenza virus A N9 subtype of different times and areaswere downloaded from the database of The National Center for Biotechnology Information (NCBI) and The Global Initiative on Sharing All Influenza Data (GISAID). MEGA 5. 05 and BioEdit softwares were used for phylogenetic tree construction and nucleotide/protein sequence analysis. Results The NA gene sequence of the novel influenza virus A/H7N9 in 2013 shared a 96% similarity with that of the H11N9 avian strain found in Czech Republic in 2010. There were 5 amino acid deletions in this novel influenza virus,and one of the new strains had a variation in potential enzymatic active sites. Conclusion The NA gene of this 2013 novel influenza virus might originate from the avian H11N9 strains detected in Czech Republic. The deletion of amino acid might result in human infection and high fatality rate.
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Objective To investigate the evolution and variations in coding amino acids of hemagglutinin (HA) gene of the novel avian influenza virus H7N9 in 2013 epidemic. Methods The HA gene sequences of influenza virus H7N9, H7N2, H7N3 and H7N7 subtypeswere downloaded from the database of The National Center for Biotechnology Information (NCBI) and The Global Initiative on Sharing All Influenza Data (GISAID). MEGA 5. 05 software was used for sequence analysis and N- J method was used for constructing the phylogenetic trees. The amino acid sequences at the receptor binding sites, glycosylation sites, and cleavage siteswas aligned and analyzed. Results The HA genes this novel A/H7N9 virus in 2013 shared a 95. 3%- 95. 6% similarity with JQ906573. 1| Zhejiang (H7N3 virus) isolated in 2011. The most important variation in this novel H7N9 isolates was found at the receptor binding site: Q226L. The 5 glycosylation sites were highly conservative. One basic amino acid (R) at the HA cleavage sites, located between aa339 and aa340, was also found in this novel isolate. Conclusion The HA gene of this novel H7N9 isolate might originate from H7 subtypes carried by birds in China. Thebinding site change caused by Q226L variation might be responsible for human infection of this novel H7N9 isolate.
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H7N9 virus is a novel avian-origin virus. The hemagglutinin (HA) and neuraminidase (NA) of the virus play key roles in the interspecies transmission, viral replication and pathogenicity. One of significant characters of H7N9 is that it has no noticeable pathogenicity among poultry, but is highly pathogenic for human being and is associated with high mortality. H7 subtype avian virus can be compatible with different NA subtypes, and has caused many infection events in human being. It can be predicted that the influence ofH7 subtype avian influenza A virus will persist and lead to serious public health problem, and therefore deserves more attention. Establishment of prevetion and control network can help to reduce the threat of H7N9 virus to human health.
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A novel avian influenza was discovered in Mainland China in March 2013, and the virus was identified as avian influenza A (H7N9)-anew virus that has not been reported previously before. Further research showed that the virus was probably a combination of three different subtypes of influenza A virus. By May 31, a total of 131 confirmed cases have been reported in China, including 39 deaths. Shanghai reported 33 confirmed cases, with the onset of 29 cases found before closing the live poultry markets by the municipal government on April 6. The onsets of the rest 4 cases were all found during the first incubation period after the closure. We found that 66. 7% (22/33) of the confirmed cases in Shanghai were above 60 years of age, and of the 15 deaths, 80% (12/15) were aged above 60 years old. It was also noted that 90. 9% (30/33) of the confirmed cases had an exposure history to susceptible animals orenvironmental circumstances. The cases appeared to be sporadic; although there were two family clusters, no evidence of human-to-human transmission has been found so far. Shanghai municipal government activated the Flu Pandemic Preparedness and Response Plan (Level IH ) onApril 2, 2013, timely after the first few cases was identified. The rapid responses of public health emergencies included citywide suspending of live poultry markets, health education, and risk communication; the epidemic was controlled effectively and timely. In this paper we analyzed the pros and cons of our prevention and control strategies, hoping to provide reference for future epidemics.
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In March 2013, death caused by infection with the novel H7N9 avian influenza virus was firstly reported in China. In addition to the viral evolution factors such as gene recombination and variation in key amino acid sites, social factors also contribute to human infection of the deadly virus. By now China still needs a standardized poultry breeding process, an orderly poultry trade market, a strong health awareness among poultry-related workers, and a strong sel--protection awareness among all citizens. Social factors may increase the chance of influenza virus transmission from birds to humans via increasing close contact. Therefore, a close joint effort of related government departments, including the agriculture, forestry, and medication, is needed for effective control and surveillance of H7N9 epidemic. The health protection and risk awareness should be upgraded among the citizens through health education. Meanwhile, research and development of influenza vaccine should be accelerated based on the surveillance data of the influenza virus evolution. Public health prophylaxis based on social influencing factors should be important in reducing the incidence of avian flu infection in human.
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Objective To understand the epidemiology and clinical features of avian influenza,improve the prophylaxis and treatment.Methods Clinical data of a fatal case caused by H7N9 avian influenza A virus in Shanghai was retrospectively reported and analyzed,literature on avian influenza A virus infection in human was reviewed.Results A severe case of H7N9 avian influenza was reported,with typical clinical characteristics.The epidemiology history of the patient was unclear,all the contacts were tested negative for H7N9 avian influenza A virus.Literature search,H7 subtype of avian influenza in 2012 was only sporadic,the majority of patients with mild symptoms.People did not have immunity against avian influenza.Conclusions Severe case of H7N9 avian influenza progress quickly and its infection pattern is not clear up-to the time point.It needs further exploration and discovery.