高致病性H7N9禽流感病毒研究进展

摘要：H7N9禽流感病毒在中国出现以来共造成5次流行。在第5次流行中出现了高致病性H7N9变异株,该病 毒株的HA链接肽位置发生了基因插入性突变,导致该病毒对家禽毒力的增强。同时在人感染H7N9禽流感病例中 也相继分离到了该病毒。因此,对高致病性H7N9禽流感病毒病原学及流行病学研究对于该疾病的预防和控制具有 重要意义。本文从高致病性H7N9禽流感病毒的变异来源、流行病学特征及防治措施等方面进行综述,为高致病性 H7N9禽流感的有效防治提供科学策略。     

1起有限人传人H7N9禽流感事件的调查

通过对1起有限人传人H7N9禽流感事件的调查,探讨人感染H7N9禽流感的流行病学特征和预防治疗措施。人感染H7N9禽流感要坚持早诊早治原则,积极治疗,加大宣传力度,提高健康水平。     

防范H7N9:不懈怠,不恐慌

禽流感又来了。这次是H7N9。连日来,上海、浙江、江苏、安徽等省市相继确诊多例H7N9禽流感患者,死亡人数不断增加。此次H7N9禽流感病毒在人类身上发现并致人死亡,系全球首次。H7N9新型病毒的突然来袭,不禁让人想起10年前的非典(SARS),不少人也担忧H7N9禽流感会成为"SARS重演"。现在,从中央有关部门到出现疫情的各地,已经进入"备战"状态。国家卫生和计生委要求,确诊人感染H7N9禽流感病例的省份启动疫情信息     

科学家发表H7N9禽流感病毒的最新研究进展

近日,中国医学科学院和北京协和医学院研究人员关于应用单克隆抗体治疗H7N9禽流感病毒的最新研究进展,这项研究对于H7N9禽流感病毒预防和治疗,预防H7N9禽流感病毒大流行具有重要意义。相关进展发表在国际学术期刊nature communication上。最近鉴定禽起源流感H7N9病毒引起严重的肺病,可能导致死亡的人类。(源自:药品资讯网)     

某院“H7N9禽流感”流行期急诊防治措施

目的探讨"H7N9禽流感"流行期医护人员应急的一系列有效防治措施。方法通过落实"H7N9禽流感"应急管理制度,加强"H7N9禽流感"的护理防治知识及施实工作。结果在"H7N9禽流感"流行期间该院内患者无交叉感染,医护人员零感染。结论 "H7N9禽流感"流行期实施医护应急防治措施能有效防止医护人员、患者之间的交叉感染并控制疫情。     

药界

H7N9禽流感病毒检测试剂盒获批 上海之江生物科技股份有限公司申报的“人感染H7N9禽流感病毒RNA检测试剂盒（荧光PCR法）”和中山大学达安基因股份有限公司申报的“人感染H7N9禽流感病毒RNA检测试剂盒（荧光PCR法）”近日获得国家食品药品监督管理总局批准，     

卫计委印发《医院人感染H7N9禽流感病毒核酸检测标准操作程序》等技术规范

根据人感染H7N9禽流感疫情联防联控工作机制会议议定事项及《关于医院开展人感染H7N9禽流感病毒核酸检测有关工作的通知》(卫办医政函〔2013〕383号,以下简称《通知》)精神,为指导医院做好人感染H7N9禽流感病毒核酸检测工作,国家卫生和计划生育委员会组织制定了《医院人感染H7N9禽流感病毒核酸检测标准     

就诊官兵H7N9禽流感预防知识知晓率调查

<正>人感染H7N9禽流感是由H7N9禽流感病毒引起的急性呼吸道传染病。全军H7N9禽流感防控会议报告指出,截止2014-02-18,共报告H7N9禽流感347例,确诊203例,超过2013年疫情高发水平。早发现、早报告、早诊断、早治疗是有效防控H7N9禽流感的关键。为维护部队战斗力,有效防控军队人员感染H7N9禽流感,强化H7N9禽流感相关知识的宣传力度,自2013年3月—2013年12月,笔者所在医     

贵州省六枝特区活禽市场禽流感感染状况调查

禽流行性感冒(简称禽流感,avian influenza,AI)被国际兽疫局定为A类传染病,同时被列入国际生物武器公约动物类传染病名单,是由A型流感病毒引起的禽类的烈性传染病,可表现为轻度的呼吸系统疾病、产蛋下降到急性致死性疾病等多种形式[1].在禽流感发现后的一百多年中,世界各地都有特定毒株引起的禽流感暴发和流行,造成高致病性禽流感大暴发的禽流感病毒都属于H5或H7亚型,高死亡率和猝死是其主要特征,并导致感染鸡群的全军覆灭.与此同时,在世界各地也不乏有中低致病力H5、H7亚型禽流感病毒的广泛流行.1992年,陈伯伦、张泽纪从广东鸡群中分离到了H9N2亚型禽流感毒株,这是我国最早报道的H9N2亚型禽流感.不论以何种致病力形式出现,不同亚型禽流感病毒,尤其是高致病力禽流感病毒引发的禽流感的暴发与流行都给养禽业造成了毁灭性的打击[2].除此之外,禽流感病毒还能感染哺乳动物甚至人,并且有着较强的感染力和致病力.因此禽流感病毒也成了一个严重危害人类生命和健康的公共卫生问题.弄清禽流感病毒的感染状况是一个亟待解决的问题.     

河北省首例人感染 H7 N9禽流感疫情流行病学调查

目的：对河北省首例人感染H7 N9禽流感病例进行流行病学调查和分析。方法描述流行病学方法和回顾性流行病学方法。结果确诊河北省首例人感染H7 N9禽流感病例,该病例经抢救无效死亡,病例有活禽市场访问史,该市场外环境1份污水H7 N9核酸检测阳性。在采取密切接触者、可疑暴露者医学观察、消毒、有关禽只无害化处理等措施后疫情得到有效控制。结论患者访问活禽市场即被感染,说明到访活禽市场是H7 N9禽流感的高危暴露因素,提示存在禽-环境-人传播,且只有少数人对该病毒存在易感性。需加强临床医师对不明原因肺炎发现能力的培训,及时启动突发公共卫生事件应急响应是疫情处置的可靠制度保障。     

表达甲型H5N1禽流感病毒结构蛋白的重组痘苗病毒的构建与鉴定

目的  构建表达甲型H5N1禽流感病毒（H5N1 avian influenza A virus,H5N1 AIAV）NIBRG14株结构蛋白的重组痘苗病毒,为研制新型人用流感疫苗奠定基础。方法  通过反转录PCR扩增H5N1 AIAV NIBRG14株的血凝素（hemagglutinin,HA）和神经氨酸酶（neuraminidase,NA）编码基因,并将改造的HA、NA基因克隆至痘苗病毒穿梭质粒 pSCCK。在重组质粒与痘苗病毒天坛株（vaccinia virus Tiantan,VTT）于Vero细胞中发生同源重组后,筛选同时表达HA和NA的重组痘苗病毒（rVTT-HA/NA）,并对其进行鉴定。结果  反转录PCR扩增的HA和NA基因大小约分别为1 700和1 400 bp,与预期相同。DNA测序证实,改造的HA和NA序列正确。对获得的rVTT-HA/NA进行PCR及测序表明,HA和NA基因正确插入VTT。蛋白质印迹显示,rVTT-HA/NA感染的Vero细胞表达的HA和NA能与相应的抗体发生反应。表达的HA具有血凝活性,血凝滴度为1∶32。结论  重组痘苗病毒rVTT-HA/NA可稳定表达H5N1 AIAV NIBRG14株的HA和NA。     

Therapeutic targeting of adenosine receptors in inflammatory diseases

A novel H7N9 avian influenza A virus (IAV) emerged in China in early 2013 causing > 450 cases of respiratory illness and 175 deaths within a 20-month period. Though avian viruses infect humans infrequently, the lack of human immunity to these viruses raises the possibility of a pandemic if they were to acquire the ability to transmit efficiently. Despite the fact that IAV pathogenicity results from the cytopathic effects and tissue damage caused by both viral replication and an overly robust immune response, current IAV therapeutics only target the viral proteins. This has led to the emergence of drug resistance due to the high mutation rates of viruses. The growing obsolescence of our current influenza therapeutics underscores the need for alternative treatment strategies. One promising area of research is the use of drugs that target the host response to IAV infection. This article describes how gene expression profiling can be used to predict drugs that reverse the destructive effects of the host response to H7N9 and other pathogenic influenza viruses.     

三种流感疫苗对H7N9禽流感病毒的免疫交叉反应

目的 评价季节性流感疫苗对H7 N9禽流感病毒的免疫效果.方法 使用3种季节性流感疫苗对受试者进行免疫接种,受试者于免疫前及免疫后21 d采集血样.应用微量血凝抑制试验(HI)对血清进行抗体检测.结果 在接种流感疫苗前,接种3种不同季节性流感疫苗的A、B、C组针对H7N9型毒株抗体几何平均滴度(GMT)均为血清1:5.0稀释阴性,保护抗体阳性率均为0.疫苗免疫后21 d,276例受试者中检测到6例受试者H7N9型毒株HI抗体结果 达到1:40阳转标准,阳转率为2.2%,A、B和C组各有2例(2.2%)、1例(1.1%)和3例(3.3%)H7N9型毒株HI抗体阳转.3组抗体阳转率差异无统计学意义(P=0.789).H7N9型抗体阳转率、GMT增长倍数、抗体保护率均未达到欧盟标准和美国食品药品管理局标准.结论 接种季节性流感疫苗不能为人群提供针对H7 N9禽流感病毒的免疫保护.     

Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses

The gene pool of influenza A viruses in aquatic birds provides all of the genetic diversity required for human and lower animals. Host range selection of the receptor binding specificity of the influenza virus hemagglutinin occurs during maintenance of the virus in different host cells that express different receptor sialo-sugar chains. In this paper, functional roles of the hemagglutinin and neuraminidase spikes of influenza viruses are described in the relation to 1) host range of influenza viruses, 2) receptor binding specificity of human and other animal influenza viruses, 3) recognition of sialyl sugar chains by Spanish influenza virus hemagglutinin, 4) highly pathogenic and potentially pandemic H5N1, H9N2, and H7N7 avian influenza viruses and molecular mechanism of host range variation of influenza viruses, 5) role of the neuraminidase spike for the host range of influenza viruses, and 6) Development of anti-influenza drugs.     

Avian influenza: a review.

PURPOSE: A review of the avian influenza A/H5N1 virus, including human cases, viral transmission, clinical features, vaccines and antivirals, surveillance plans, infection control, and emergency response plans, is presented. SUMMARY: The World Health Organization (WHO) considers the avian influenza A/H5N1 virus a public health risk with pandemic potential. The next human influenza pandemic, if caused by the avian influenza A/H5N1 virus, is estimated to have a potential mortality rate of more than a hundred million. Outbreaks in poultry have been associated with human transmission. WHO has documented 258 confirmed human infections with a mortality rate greater than 50%. Bird-to-human transmission of the avian influenza virus is likely by the oral-fecal route. The most effective defense against an influenza pandemic would be a directed vaccine to elicit a specific immune response toward the strain or strains of the influenza virus. However, until there is an influenza pandemic, there is no evidence that vaccines or antivirals used in the treatment or prevention of such an outbreak would decrease morbidity or mortality. Surveillance of the bird and human populations for the highly pathogenic H5N1 is being conducted. Infection-control measures and an emergency response plan are discussed. CONCLUSION: Avian influenza virus A/H5N1 is a public health threat that has the potential to cause serious illness and death in humans. Understanding its pathology, transmission, clinical features, and pharmacologic treatments and preparing for the prevention and management of its outbreak will help avoid its potentially devastating consequences.     

Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives

Catechin derivatives with different alkyl chain length and aromatic ring substitutions at the 3-hydroxyl group were synthesized from epigallocatechin (EGC) and (+)-catechin (C) and their anti-influenza viral activity were evaluated in vitro and in ovo. Pronounced antiviral activity was observed for derivatives carrying moderate chain length (7-9 carbons) as compared to those with aromatic rings, whereas the 5'-hydroxyl group of the trihydroxy benzyl moiety did not significantly contribute to antiviral activity. The derivatives exerted inhibitory effects for all six influenza subtypes tested including three major types of currently circulating human influenza viruses (A/H1N1, A/H3N2 and B type), H2N2 and H9N2 avian influenza virus. The compounds strongly inhibited adsorption of the viruses on red blood cell (RBC). They also restricted the growth of avian influenza virus in ovo with minimum inhibition concentration (MIC) of 5-10 microM far exceeding the neuraminidase (NA) inhibitor oseltamivir or M2 proton channel inhibitor amantadine. The antiviral activity appears to be mediated by interaction with hemagglutinin (HA)/viral membrane rendering HA less fusogenic at the initial stage of infection. The broad spectrum activity against various subtypes of influenza viruses may complement the limitations of current antivirals and contribute for managing potentially emerging influenza pandemic. The structure-activity data of catechin derivatives may usefully guideline future research endeavors for applying green tea catechins as alternative anti-viral agents.     

Characteristics of human infection with avian influenza viruses and development of new antiviral agents

Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths. The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains. The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms. The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection. Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc. In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV.     

The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses

In 1997, an H5N1 avian influenza A/Hong Kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. In 1999, another avian A/Hong/1074/99 (H9N2) virus caused influenza in two children. In such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. Here we demonstrate the efficacy of the neuraminidase inhibitor GS4104 (oseltamivir phosphate) against these H5N1 and H9N2 viruses. GS4071 (the active metabolite of oseltamivir) inhibited viral replication in MDCK cells (EC(50) values, 7.5-12 microM) and neuraminidase activity (IC(50) values, 7.0-15 nM). When orally administered at doses of 1 and 10 mg/kg per day, GS4104 prevented death of mice infected with A/Hong Kong/156/97 (H5N1), mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2), or human A/Hong Kong/1074/99 (H9N2) viruses and reduced virus titers in the lungs and prevented the spread of virus to the brain of mice infected with A/Hong Kong/156/97 (H5N1) and mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2) viruses. When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control. Oral administration of GS4104 (0.1 mg/kg per day) in combination with rimantadine (1 mg/kg per day) reduced the number of deaths of mice infected with 100 MLD(50) of H9N2 virus and prevented the deaths of mice infected with 5 MLD(50) of virus. Thus, GS4104 is efficacious in treating infections caused by H5N1 and H9N2 influenza viruses in mice.