埃博拉病毒

·编者按·

2014年2月埃博拉病毒在几内亚境内爆发，并先后波及利比里亚、塞拉利昂、尼日利亚、塞内加尔、美国、西班牙、马里等七国.埃博拉病毒是埃博拉病毒病（曾称埃博拉出血热）的病原体，在1976年中非地区暴发的疫情中首次被发现.到目前为止，已确认的埃博拉病毒属包括5个种，本次西非疫情的病原体为扎伊尔型埃博拉病毒，基因序列分析显示，与既往疫情的扎伊尔型埃博拉病毒同源性为97%，存在一定的变异.根据世界卫生组织公布的统计结果显示，截止2014年11月15日，全球已有共计15145人感染埃博拉病毒，其中5420人死亡.此次埃博拉病毒疫情爆发的感染及死亡人数都达到历史最高.2014年11月10日，国际组织“无国界医生”宣布，利比里亚感染埃博拉病毒的病例首次减少，但同时指出这并不意味着疫情结束.

目前，对抗埃博拉病毒的方法主要是注射NPC1阻碍剂，但是NPC1蛋白于细胞间进行运输胆固醇，会阻挡胆固醇的运输路线，造成尼曼匹克症.治疗性抗体（ZmappTM）的研究也在积极开展中，2名感染埃博拉病毒的美国医护人员接受了实验性药物的治疗，从效果来看，两人所患的埃博拉出血热可以得到治愈.日本新研制的抗流感药物法匹拉韦（Favipivir）也对埃博拉病毒病有一定的治疗效果.2014年11月26日，美国国家卫生研究院宣布，首个埃博拉疫苗cADV-EBOV成功通过临床试验.加拿大研制的VSV-EBOV疫苗也已经开展人体临床试验.2014年8月，我国军事医学科学院生物流行病研究所历时5年研制的对抗埃博拉病毒的药物“jk-05”，通过总后卫生部专家评审，获得军队特需药品批件.2014年9月，中国疾病预防控制中心病毒病所成功研制埃博拉病毒核酸、抗原和抗体检测试剂.中国疾控中心派出的实验室检测队携带了该检测试剂，并利用该试剂在塞拉利昂开展病毒检测任务.

为了展示与埃博拉病毒研究相关的重要参考文献、科技期刊、研究机构、科研人员，系统全面地描述埃博拉病毒的来龙去脉，帮助研究人员更便捷地开展相关工作，特组织本专题.

本专题得到了高福院士（中国疾控中心副主任、中国科学院病原微生物与免疫学重点实验室主任、中国科学院微生物研究所研究员）的大力支持.

·热点数据排行·

截止2014年11月27日，中国知网（CNKI）和Web of Science的数据报告显示，有关埃博拉病毒研究的期刊文献分别为231与1373条，本刊将相关数据按照：机构发文数、作者发文数、期刊发文数、被引用频次进行排行，结果如下.

热点追踪

埃博拉病毒

·编者按·

2014年2月埃博拉病毒在几内亚境内爆发，并先后波及利比里亚、塞拉利昂、尼日利亚、塞内加尔、美国、西班牙、马里等七国.埃博拉病毒是埃博拉病毒病（曾称埃博拉出血热）的病原体，在1976年中非地区暴发的疫情中首次被发现.到目前为止，已确认的埃博拉病毒属包括5个种，本次西非疫情的病原体为扎伊尔型埃博拉病毒，基因序列分析显示，与既往疫情的扎伊尔型埃博拉病毒同源性为97%，存在一定的变异.根据世界卫生组织公布的统计结果显示，截止2014年11月15日，全球已有共计15145人感染埃博拉病毒，其中5420人死亡.此次埃博拉病毒疫情爆发的感染及死亡人数都达到历史最高.2014年11月10日，国际组织“无国界医生”宣布，利比里亚感染埃博拉病毒的病例首次减少，但同时指出这并不意味着疫情结束.

目前，对抗埃博拉病毒的方法主要是注射NPC1阻碍剂，但是NPC1蛋白于细胞间进行运输胆固醇，会阻挡胆固醇的运输路线，造成尼曼匹克症.治疗性抗体（ZmappTM）的研究也在积极开展中，2名感染埃博拉病毒的美国医护人员接受了实验性药物的治疗，从效果来看，两人所患的埃博拉出血热可以得到治愈.日本新研制的抗流感药物法匹拉韦（Favipivir）也对埃博拉病毒病有一定的治疗效果.2014年11月26日，美国国家卫生研究院宣布，首个埃博拉疫苗cADV-EBOV成功通过临床试验.加拿大研制的VSV-EBOV疫苗也已经开展人体临床试验.2014年8月，我国军事医学科学院生物流行病研究所历时5年研制的对抗埃博拉病毒的药物“jk-05”，通过总后卫生部专家评审，获得军队特需药品批件.2014年9月，中国疾病预防控制中心病毒病所成功研制埃博拉病毒核酸、抗原和抗体检测试剂.中国疾控中心派出的实验室检测队携带了该检测试剂，并利用该试剂在塞拉利昂开展病毒检测任务.

为了展示与埃博拉病毒研究相关的重要参考文献、科技期刊、研究机构、科研人员，系统全面地描述埃博拉病毒的来龙去脉，帮助研究人员更便捷地开展相关工作，特组织本专题.

本专题得到了高福院士（中国疾控中心副主任、中国科学院病原微生物与免疫学重点实验室主任、中国科学院微生物研究所研究员）的大力支持.

·热点数据排行·

截止2014年11月27日，中国知网（CNKI）和Web of Science的数据报告显示，有关埃博拉病毒研究的期刊文献分别为231与1373条，本刊将相关数据按照：机构发文数、作者发文数、期刊发文数、被引用频次进行排行，结果如下.

国内机构发文数量排名 　　国外机构发文数量排名

国内期刊发文数量排名 　　国外期刊发文数量排名

根据中国知网（CNKI）数据报告，有关埃博拉病毒研究的高被引论文排行结果如下.

国内数据库高被引论文排行

根据Web of Science统计数据，有关埃博拉病毒研究的高被引论文排行结果如下.

国外数据库高被引论文排行

（续表）

·高被引论文摘要·

被引频次：10

埃博拉病毒的研究概况

杨涛

随着研究的深入，埃博拉病毒逐渐被人类所认识.本文着重介绍了埃博拉病毒的一般特性、流行病学特性、埃博拉出血热的发病机理、临床表现和防治及其最新研究进展，对人们了解埃博拉病毒和开发抗埃博拉病毒的药物与疫苗起到指导作用.

埃博拉病毒；埃博拉出血热；病毒基因；丝状病毒属；自身免疫应答；丝状病毒科；病毒株；单股负链；自然宿主；表面蛋白

来源出版物：国际病毒学杂志， 2002， 9（5）: 152-155

被引频次：9

抗埃博拉病毒VP40蛋白单克隆抗体的制备及在抗原捕捉ELISA中的应用

王淑杰，王喜军，胡森，等

摘要：本研究以原核表达、纯化的扎伊尔株埃博拉病毒（Ebola virus， EBOV）VP40蛋白片段免疫BALB/c小鼠，通过杂交瘤技术制备单克隆抗体，获得一株分泌抗EBOV VP40蛋白单克隆抗体的杂交瘤细胞系.以重组杆状病毒表达EBOV VP40蛋白为抗原，经Western blot和间接免疫荧光检测该单克隆抗体显示出良好的特异性免疫反应.采用该株杂交瘤细胞系经腹腔注射接种8日龄BALB/c小鼠，制备腹水，并经纯化和HRP标记，获得HRP标记的抗EBOV VP40蛋白单克隆抗体.从而，初步建立一种抗原捕捉ELSIA诊断方法，以原核表达EBOV VP40蛋白片段兔抗血清为一抗，应用HRP标记的抗EBOV VP40蛋白单克隆抗体检测杆状病毒表达的重组EBOV VP40蛋白显示出良好的敏感性和特异性.结果表明，初步建立的抗原捕捉ELSIA诊断方法有希望成为一种理想的检测EBOV感染的诊断方法.

关键词：Ebola病毒；VP40蛋白；单克隆抗体

来源出版物：中国预防兽医学报， 2008，30（4）: 309-313 联系邮箱：王淑杰，zgb@hvri.ac.cn

被引频次：7

埃博拉出血热及埃博拉病毒的研究进展

许黎黎，张连峰

摘要：埃博拉病毒可以引起一种人畜共患烈性传染病，即埃博拉出血热，此病于1976年始发于埃博拉河流域，并且于该区域严重流行，故而得名.人类一旦感染埃博拉病毒，死亡率可高达88%，从而引起医学界的广泛关注，世界卫生组织已将埃博拉病毒列为对人类危害最为严重的病毒之一.深入地了解埃博拉出血热及埃博拉病毒，及其致病机理，对于埃博拉出血热的预防和控制具有非常重要的意义.

关键词：埃博拉出血热；埃博拉病毒

来源出版物：中国比较医学杂志， 2011， 21（1）: 70-74 联系邮箱：张连峰，lianfeng_zhang3@yahoo.com.cn

被引频次：436

来源出版物：Nature Medicine， 2001， 7（12）: 1313-1319

被引频次：383

Development of a preventive vaccine for Ebola virus infection in primates

Sullivan， NJ； Sanchez， A； Rollin， PE； et al.

Abstract: Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype， one of four strains identified to date（1，2）. Its rapid progression allows little opportunity to develop natural immunity， and there is currently no effective anti-viral therapy. Therefore，vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic，wild-type， 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls， who progressed to a moribund state and death in less than one week. In contrast， all vaccinated animals were asymptomatic for more than six months， with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates.

Keywords: T-cell induction； protective efficacy； immune-responses； recombinant； immunization； adenovirus； protein； malaria； immunogenicity； therapy

来源出版物：Nature， 2000， 408（6812）: 605-609

被引频次：340

Fruit bats as reservoirs of Ebola virus

Eric M. Leroy； Brice Kumulungui； Xavier Pourrut

Abstract: The first recorded human outbreak of Ebola virus was in 1976， but the wild reservoir of this virus is still unknown. Here we test for Ebola in more than a thousand small vertebrates that were collected during Ebola outbreaks in humans and great apes between 2001 and 2003 in Gabon and the Republic of the Congo. We find evidence of asymptomatic infection by Ebola virus in three species of fruit bat，indicating that these animals may be acting as a reservoir for this deadly virus.

Keywords: decline； Africa

来源出版物：Nature， 438（7068）: 575-576 联系邮箱：Leroy， EM； eric.leroy@ird.fr

被引频次：297

C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans

Alvarez， CP； Lasala， F； Carrillo， J； et al.

Abstract: Ebola virus is a highly lethal pathogen responsible for several outbreaks of hemorrhagic fever. Here we show that the primate lentiviral binding C-type lectins DC-SIGN and L-SIGN act as cofactors for cellular entry by Ebola virus. Furthermore， DC-SIGN on the surface of dendritic cells is able to function as a trans receptor， binding Ebola virus-pseudotyped lentiviral particles and transmitting infection to susceptible cells. Our data underscore a role for DC-SIGN and L-SIGN in the infective process and pathogenicity of Ebola virus infection.

Keywords: immunodeficiency-virus； receptor； protein； cells； identification； expression； infection； lines

来源出版物：Journal of Virology， 2002， 76（13）: 6841-6844

被引频次：281

Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection

Chandran， K； Sullivan， NJ； Felbor， U； et al.

Abstract: Ebola virus （EboV） causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney （Vero） cells by vesicular stornatitis viruses bearing the EboV gtycoprotein （GP） requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines， we identified an essential role for cathepsin B （CatB） and an accessory role for cathepsin L （CatL） in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs.

Keywords: envelope glycoprotein； cathepsin-B； influenza hemagglutinin； membrane-fusion； inhibitors； cysteine；entry； proteinases； cells；mice

来源出版物：Science， 2005， 308（5728）: 1643-1645 联系邮箱：Cunningham， JM； jcunningham@rics.bwh.harvard.edu

被引频次：268

A system for functional analysis of Ebola virus glycoprotein

Takada， A； Robison， C； Goto， H； et al.

Abstract: Ebola virus causes hemorrhagic fever in humans and nonhuman primates， resulting in mortality rates of up to 90%. Studies of this virus have been hampered by its extraordinary pathogenicity， which requires biosafety level 4 containment. To circumvent this problem，we developed a novel complementation system for functional analysis of Ebola virus glycoproteins， It relies on a recombinant vesicular stomatitis virus （VSV） that contains the green fluorescent protein gene instead of the receptor-binding G protein gene （VSV Delta G*）. Herein we show that Ebola Reston virus glycoprotein （ResGP） is efficiently incorporated into VSV particles. This recombinant VSV with integrated ResGP （VSV Delta G*-ResGP） infected primate cells more efficiently than any of the other mammalian or avian cells examined，in a manner consistent with the host range tropism of Ebola virus， whereas VSV Delta G* complemented with VSV G protein （VSV Delta G*-G） efficiently infected the majority of the cells tested. We also tested the utility of this system for investigating the cellular receptors for Ebola virus. Chemical modification of cells to alter their surface proteins markedly reduced their susceptibility to VSV Delta G*-ResGP but not to VSV Delta G*-G. These findings suggest that cell surface glycoproteins with N-linked oligosaccharide chains contribute to the entry of Ebola viruses， presumably acting as a specific receptor and/or cofactor for virus entry. Thus， our VSV system should be useful for investigating the functions of glycoproteins from highly pathogenic viruses or those incapable of being cultured in vitro.

Keywords: vesicular stomatitis-virus； marburg virus； expression； cells； replication； protein； gene； elements； receptor； entry

来源出版物：Proceedings of The National Academy of Sciences of The United States of America， 1997， 94（26）: 14764-14769

联系邮箱：Kawaoka， Y； kawaokay@svm.vetmed.wisc.edu

被引频次：263

Crystal structure of the Ebola virus membrane fusion subunit， GP2， from the envelope glycoprotein ectodomain

Weissenhorn， W； Carfi， A； Lee， KH； et al.

Abstract: We have determined the structure of GP2 from the Ebola virus membrane fusion glycoprotein by X-ray crystallography. The molecule contains a central triple-stranded coiled coil followed by a disulfide-bonded loop homologous to an immunosuppressive sequence in retroviral glycoproteins， which reverses the chain direction and connects to an a helix packed antiparallel to the core helices. The struc-ture suggests that fusion peptides near the N termini form disulfide-bonded loops at one end of the molecule and that the C-terminal membrane anchors are at the same end. In this conformation， GP2 could both bridge two membranes and facilitate their apposition to initiate membrane fusion. We also find a heptad irregularity like that in low-pH-induced influenza HA2 and a solvent ion trapped in a coiled coil like that in retroviral TMs.

Keywords: influenza-virus； marburg virus； HIV-1 GP41； conformational-changes； electron-microscopy； escherichia-coli； atomic-structure；coiled coils； hemagglutinin； protein

来源出版物：Molecular Cell， 1998， 2（5）: 605-616

被引频次：255

Lipid raft microdomains: A gateway for compartmentalized trafficking of Ebola and Marburg viruses

Bavari， S； Bosio， CM； Wiegand， E； et al.

Abstract: Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here， we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules， suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous， virus-like particles （VLPs）， strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts， identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses.

Keywords: filovirus； Ebola； rafts； budding； VLP

来源出版物：Journal of Experimental Medicine， 2002， 195（5）: 593-602

被引频次：251

The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing

Sanchez， A； Trappier， SG； Mahy， BWJ； et al.

Abstract: In late 1994 and early 1995， Ebola （EBO） virus dramatically reemerged in Africa， causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein （130 kDa） is encoded in two reading frames， which are linked by transcriptional editing. This editing results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller （50-70 kDa）， nonstructural， secreted glycoprotein， which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new （fourth） subtype of EBO virus， In contrast， the EBO virus isolate from the 1995 outbreak in Kikwit， Zaire， is virtually identical to the virus that caused a similar epidemic in Yambuku， Zaire， almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild.

Keywords: filovirus； glycoprotein gene； phylogenetic analysis

来源出版物：Proceedings of The National Academy of Sciences of The United States of America， 1996， 93（8）: 3602-3607

被引频次：246

Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates

Sullivan， NJ； Geisbert， TW； Geisbert， JB； et al.

Abstract: Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease（1）， more than six months was required to complete the immunizations，making it impractical to limit an acute epidemic. Here， we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral （ADV） vector encoding the Ebola glycoprotein （GP） was induced more rapidly than with DNA priming and ADV boosting， but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease， cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein （NP） vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8（+）T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later， they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola， and is applicable to other viruses.

Keywords: passive transfer； infection； glycoproteins； cytotoxicity； injury； gene

来源出版物：Nature， 2003， 424（6949）: 681-684

·最新论文推荐·

埃博拉病毒病：流行病学、生态学、诊断、治疗及控制

李昱，任翔，刘翟，等

摘要：埃博拉病毒（Ebolavirus）是埃博拉病毒病（Ebola Virus Disease，EVD）的病原体，1976年首次在非洲发现，目前确认该病毒包括5个种，其中苏丹型（Sudan ebolavirus）、扎伊尔型（Zaire ebolavirus）、塔伊森林型（Ta Forest ebolavirus）和本迪布焦型（Bundibugyo ebolavirus）均有感染人发病的记录；莱斯顿型（Reston ebolavirus）可致人隐性感染，并与多起猕猴暴发疫情有关，曾在菲律宾的猪中检出.人类埃博拉病毒病的病死率为25%～90%，疫情均发生在非洲，主要集中在10°N—10°S的非洲地区，本次西非疫情是规模最大的暴发流行，截至2014年8月20日已报告2615例病例.该病是动物源性传染病，目前证据支持果蝠可能为病毒的自然储存宿主.该病在人群中主要通过接触传播，有症状的病人才具有传染性.未采取正确防护措施的医护人员、家庭护理人员及接触病人血液、体液，或接触病人血液、体液等污染的物品，或接触病例尸体的人是高风险感染人群.本病起病急，早期表现为发热、厌食、虚弱无力等非特异性症状，可通过检测病毒核酸、抗原、抗体等方法确诊.目前尚无批准上市的特效药和疫苗，以对症和支持治疗为主.预防控制策略主要包括早期发现病例、及时调查处置、追踪和密切观察接触者，以及有效的医院内和社区的感染控制.

关键词：埃博拉病毒病；埃博拉病毒；流行病学

来源出版物：科技导报， 2014， 32（24）: 15-24 联系邮箱：余宏杰，yuhj@chinacdc.cn

埃博拉病毒病：病原学、致病机制、治疗与疫苗研究进展

程颖，刘军，李昱，等

摘要：2013年12月始，埃博拉病毒病在几内亚、利比里亚、塞拉利昂和尼日利亚4国暴发.其病原体——埃博拉病毒（Ebolavirus）于1976年被首次分离，为单股负链、不分节段、有囊膜的RNA病毒，属丝状病毒科，分5种，包括扎伊尔型、苏丹型、本迪布焦型、塔伊森林型和莱斯顿型.其基因顺序为3′端-NP-VP35-VP40-GP-VP30-VP24-L-5′端.埃博拉病毒属于 A类病原，致病能力极强，操作活病毒需在生物安全4级实验室进行.其主要靶细胞是血管内皮细胞、肝细胞、巨噬细胞和树突状细胞等，通过抑制天然和获得性免疫应答反应，增加血管通透性，引起肝脏等多脏器损伤，引发发热、出血、多器官功能衰竭和休克等症状.目前尚无批准上市的特异治疗药物和疫苗，处于研发或临床试验阶段的治疗药物包括：（ⅰ）抗流感病毒药物T-705可能阻碍埃博拉病毒在细胞内增殖，从而遏制感染；（ⅱ）ZMapp包含3种人源化的单克隆抗体，属优化的鸡尾酒疗法；（ⅲ）基于RNA干扰的基因治疗药物TKM-Ebola；（ⅳ）凝血调节因子、炎性介质制剂，如源于丝虫的抗凝蛋白 rNAPc2等.处于研发阶段的疫苗有：（ⅰ）复制缺陷型疫苗，安全性好，但诱导免疫的时间较长；（ⅱ）减毒复制型疫苗，效果好，但存在安全隐患.开展深入的病原学、免疫病理和致病机制研究，将有利于治疗药物和疫苗的研发.同时，应推进有希望的治疗方案和疫苗进入人体临床试验阶段.

关键词：埃博拉病毒；基因组；免疫；致病机制；治疗药物；疫苗

来源出版物：科学通报， 2014， 59（30）: 2889-2989

双重荧光RT-PCR检测4种致病性亚型埃博拉病毒方法的建立

式中，bi是得分向量，它包含着不同样本之间的信息关系，pi是加载向量，它包含着不同变量之间的信息关系，p是独立变量的个数，G是剩余矩阵。

钟玉清，郑夔，苏锦坤，等

摘要：目的 建立可同时检测苏丹、扎伊尔、本迪布焦和科特迪瓦4种致病性亚型埃博拉病毒的双重荧光RT-PCR检测方法.方法 根据4种致病性亚型埃博拉病毒的核蛋白NP基因保守序列，针对苏丹型/扎伊尔型病毒以及针对本迪布焦型/科特迪瓦型病毒，相应设计2套引物和探针.以体外转录的4种亚型埃博拉病毒 RNA为模板，进行条件的优化以及方法特异性、灵敏度、重复性试验，建立双重荧光RT-PCR检测方法.结果 新建立的双重荧光RT-PCR方法检测只对4种埃博拉病毒阳性对照RNA模板有特异性扩增，与肾综合征出血热病毒、登革病毒、黄热病毒、西尼罗病毒、日本脑炎病毒、基孔肯雅病毒均无交叉反应，2套引物和探针的检测灵敏度均可达到最低50拷贝/μL.苏丹型和本迪布焦型埃博拉病毒阳性对照RNA模板的4种稀释度（2×108、2×106、2×104、2×102拷贝/μL）重复检测3次均有较好的重复性.结论 建立的方法能同时检测上述4种亚型埃博拉病毒，灵敏度高，特异性强，可用于埃博拉病毒疑似病例的检测.

关键词：埃博拉病毒；聚合酶链反应

来源出版物：华南预防医学， 2014， 40 （5）: 416-420

埃博拉病毒感染及其实验室检查

林迪，孙长贵

摘要：据世界卫生组织官方报道，截至2014年8月4日埃博拉病毒累计感染1711人，并致932人死亡.埃博拉病毒是一种能引起人类和灵长类动物产生埃博拉出血热的烈性传染病病毒，该病毒致死率极高，为50%～90%.本文就该病毒的结构、生物学特性、流行病学、临床表现、诊断与鉴别诊断和实验室检查等作简要综述.

关键词：埃博拉病毒；出血热；流行病学；感染

来源出版物：试验与检验医学， 2014， 32（5）: 495-497

埃博拉病毒NP抗原表位区段的克隆和表达

王晓丹，李鹏飞，冯晓燕，等

摘要：目的 分析埃博拉病毒核蛋白（NP）抗原表位，克隆表达埃博拉病毒 NP抗原，为免疫学诊断试剂的研究奠定基础.方法 采用BioSun生物学软件预测分析埃博拉病毒NP抗原的氨基酸表位区间，采用大肠杆菌优势密码子反向翻译成基因序列，采用PCR退火合成法合成NP优势密码子抗原基因，并利用载体pBVIL1进行克隆表达.采用间接ELISA技术评价获得NP抗原的特异性.结果 确定埃博拉病毒NP抗原的氨基酸表位位于360～739 aa，共设计36条引物，扩增合成1140 bp的NP抗原基因，克隆表达后，融合蛋白相对分子质量为58×103，测序结果显示插入的NP基因正确.初步结果显示，NP抗原的特异性为99.24%（130/131）.结论获得埃博拉病毒NP抗原，为进一步研制特异的埃博拉病毒快速诊断试剂提供了抗原储备.

来源出版物：军事医学， 2014， 38（9）: 659-662

从《伤寒论》少阴病思考埃博拉出血热辨治策略

刘清泉

摘要：世界卫生组织日前宣布非洲埃博拉出血热疫情为“国际关注的突发公共卫生事件”，国家卫生和计划生育委员会发布了《埃博拉出血热防控方案》.尽管目前中医对埃博拉出血热病没有治疗经验可谈，但是在历史上，中医曾多次参与“出血热”疫情的控制与治疗，并获得良效.从发病表现上，埃博拉出血热符合《伤寒论》少阴病发病规律.埃博拉出血热本次发病多为两经并病，故病重而亡多.据此目前初步分为四期：发病初期少阴太阳并病，吐利期少阴太阴并病，出血期少阴太阳蓄血并病，厥脱期少阴厥阴并病，临床中应严密观察病情变化，观其脉证，知犯何逆，主治从少阴，兼顾热毒湿气，随证治之.

关键词：埃博拉病毒；出血热；伤寒论；少阴病

来源出版物：中医杂志， 2014， 55 （18）: 1555-1557

西非埃博拉出血热的五运六气分析

顾植山

摘要：目的：探讨中医对当前西非埃博拉疫情的治疗方法.方法：从中医的五运六气和伏气理论分析当前西非埃博拉出血热的病因病机、治法治则和遣方用药特点.结果：当前的西非埃博拉疫情与五运六气及伏气因素有关，其病机重点在伏寒伤阳；论治可以《伤寒论》少阴病篇有关条文为主要依据，宣发少阴伏邪，慎用清热解毒重剂，亦可参考今年的三因司天运气方附子山萸汤和正阳汤.结论：运气失常是发生埃博拉疫情的重要原因，加强中医运气学说研究对西非埃博拉出血热的防治具有重要意义.

关键词：埃博拉病毒；疫情；西非；五运六气

来源出版物：浙江中医大学学报， 2014， 38 （9）: 1041-1043

Ebola Virus Disease in West Africa - The First 9 Months of the Epidemic and Forward Projections

Aylward， Bruce； Barboza， Philippe； Bawo， Luke； et al.

Abstract: BACKGROUND On March 23， 2014， the World Health Organization （WHO） was notified of an outbreak of Ebola virus disease （EVD） in Guinea. On August 8， the WHO declared the epidemic to be a "public health emergency of international concern." METHODS By September 14， 2014， a total of 4507 probable and confirmed cases， including 2296 deaths from EVD （Zaire species） had been reported from five countries in West Africa - Guinea， Liberia， Nigeria， Senegal， and Sierra Leone. We analyzed a detailed subset ofdata on 3343 confirmed and 667 probable Ebola cases collected in Guinea， Liberia， Nigeria， and Sierra Leone as of September 14. RESULTS The majority of patients are 15 to 44 years of age （49.9% male）， and we estimate that the case fatality rate is 70.8% （95% confidence interval ［CI］， 69 to 73） among persons with known clinical outcome of infection. The course of infection， including signs and symptoms， incubation period （11.4 days）， and serial interval （15.3 days）， is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth， the estimated basic reproduction numbers （R-0） are 1.71 （95% CI， 1.44 to 2.01） for Guinea， 1.83 （95% CI， 1.72 to 1.94） for Liberia， and 2.02 （95% CI， 1.79 to 2.26） for Sierra Leone. The estimated current reproduction numbers （R） are 1.81 （95% CI， 1.60 to 2.03） for Guinea， 1.51 （95% CI， 1.41 to 1.60） for Liberia， and 1.38 （95% CI， 1.27 to 1.51） for Sierra Leone；the corresponding doubling times are 15.7 days （95% CI， 12.9 to 20.3） for Guinea， 23.6 days （95% CI， 20.2 to 28.2） for Liberia， and 30.2 days （95% CI， 23.6 to 42.3） for Sierra Leone. Assuming no change in the control measures for this epidemic， by November 2， 2014， the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea， 9890 in Liberia， and 5000 in Sierra Leone， exceeding 20，000 in total. CONCLUSIONS These data indicate that without drastic improvements in control measures， the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months Keywords: hemorrhagic-fever； clinical-observations； congo； outbreak； kikwit； zaire； transmission； uganda

来源出版物：New England Journal of Medicine， 2014， 371（16）: 1481-1495 联系邮箱：Donnelly， CA； c.donnelly@imperial.ac.uk

Emergence of Zaire Ebola Virus Disease in Guinea

Baize， Sylvain； Pannetier， Delphine； Oestereich， Lisa； et al.

Abstract: In March 2014， the World Health Organization was notified of an outbreak of a communicable disease characterized by fever，severe diarrhea， vomiting， and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus （EBOV） as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea.

Keywords: hemorrhagic-fever； lassa-virus； filoviruses； infection； models； assay

来源出版物：New England Journal of Medicine， 2014， 371（15）: 1418-1425 联系邮箱：Gunther， S； guenther@bni.uni-hamburg.de

Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp

Qiu， Xiangguo； Wong， Gary； Audet， Jonathan； et al.

Abstract: Without an approved vaccine or treatments， Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches， however， have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies （ZMapp）， optimized from two previous antibody cocktails， is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever， viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease， as indicated by elevated liver enzymes，mucosal haemorrhages and generalized petechia could be reversed， leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far，and results warrant further development of this cocktail for clinical use.

Keywords: monoclonal-antibodies； hemorrhagic-fever； postexposure protection； mediated protection； guinea-pigs； infection； challenge

来源出版物：Nature， 2014， 514（7520）: 47-53 联系邮箱：Zeitlin， L； larry.zeitlin@mappbio.com

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

Gire， Stephen K； Goba， Augustine； Andersen， Kristian G.； et al.

Abstract: In its largest outbreak， Ebola virus disease is spreading through Guinea， Liberia， Sierra Leone， and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to similar to 2000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation， allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004， crossed from Guinea to Sierra Leone in May 2014， and has exhibited sustained human-to-human transmission subsequently， with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets， they should be monitored for impact on diagnostics， vaccines， and therapies critical to outbreak response.

Keywords: purifying selection； hemorrhagic-fever； dengue virus； polymerase； RNA

来源出版物：Science， 2014， 345（6202）: 1368-1372 联系邮箱：Goba， A； augstgoba@yahoo.com

Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability

Escudero-Pérez B； Volchkova VA； Dolnik O； et al.

Abstract: During Ebola virus （EBOV） infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP， both expressed from the same GP gene， have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines （TNFα， IL1β， IL6， IL8， IL12p40， and IL1-RA， IL10）. Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40， CD80， CD83 and CD86. Contrary to shed GP， secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study， we show that shed GP activity is likely mediated through cellular toll-like receptor 4 （TLR4） and is dependent on GPglycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shedGP activity is negated upon addition of mannose-binding sera lectin MBL， a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore， we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly， demonstrating the interplay between shed GP， systemic cytokine release and increased vascular permeability. In conclusion， shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascularpermeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity.

来源出版物：PLoS Pathogens， 2014， 10（11）: e1004509

Evaluating Ebola Therapies — The Case for RCTs

Cox E； Borio L； Temple R

Abstract: The worst Ebola epidemic in history is ongoing. With the number of deaths from Ebola virus disease （EVD） already in the thousands and predicted to rise to tens of thousands， 1 the situation is tragic. No treatments have yet been shown to be safe and effective in ptients with EVD. Some candidate therapies have shown benefit in animal models of infection， and others have shown activity against certain Ebola strains in cell culture， but concerns have been raised about possible toxicity of some of these agents. There is an urgent need to identify therapies that are effective and safe， and well-designed.

来源出版物：The New England journal of medicine， published on December 3， 2014， at NEJM.org

（责任编辑 王帅帅，卫夏雯）

HIV-I and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress

Martin-Serrano， J； Zang， T； Bieniasz， PD

Retroviral Gag proteins encode sequences， termed late domains， which facilitate the final stages of particle budding from the plasma membrane. We report here that interactions between Tsg101， a factor involved in endosomal protein sorting， and short peptide motifs in the HIV-1 Gag late domain and Ebola virus matrix （EbVp40） proteins are essential for efficient egress of HIV-1 virions and Ebola virus-like particles. EbVp40 recruits Tsg101 to sites of particle assembly and a short， EbVp40-derived Tsg101-binding peptide sequence can functionally substitute for the HIV-1 Gag late domain. Notably， recruitment of Tsg101 to assembling virions restores budding competence to a late-domain-defective HIV-1 in the complete absence of viral late domain. These studies define an essential virus-host interaction that is conserved in two unrelated viruses. Because the Tsg101 is recruited by small， conserved viral sequence motifs， agents that mimic these structures are potential inhibitors of the replication of these lethal human pathogens.

rous-sarcoma virus； vesicular stomatitis-virus； proline-rich motif； Gag polyprotein； matrix protein； ubiquitin ligase； type-1；domain； release； replication