埃博拉病毒

·編者按·

2014年2月埃博拉病毒在幾內(nèi)亞境內(nèi)爆發(fā)，并先后波及利比里亞、塞拉利昂、尼日利亞、塞內(nèi)加爾、美國、西班牙、馬里等七國.埃博拉病毒是埃博拉病毒?。ㄔQ埃博拉出血熱）的病原體，在1976年中非地區(qū)暴發(fā)的疫情中首次被發(fā)現(xiàn).到目前為止，已確認的埃博拉病毒屬包括5個種，本次西非疫情的病原體為扎伊爾型埃博拉病毒，基因序列分析顯示，與既往疫情的扎伊爾型埃博拉病毒同源性為97%，存在一定的變異.根據(jù)世界衛(wèi)生組織公布的統(tǒng)計結(jié)果顯示，截止2014年11月15日，全球已有共計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發(fā)的感染及死亡人數(shù)都達到歷史最高.2014年11月10日，國際組織“無國界醫(yī)生”宣布，利比里亞感染埃博拉病毒的病例首次減少，但同時指出這并不意味著疫情結(jié)束.

目前，對抗埃博拉病毒的方法主要是注射NPC1阻礙劑，但是NPC1蛋白于細胞間進行運輸膽固醇，會阻擋膽固醇的運輸路線，造成尼曼匹克癥.治療性抗體（ZmappTM）的研究也在積極開展中，2名感染埃博拉病毒的美國醫(yī)護人員接受了實驗性藥物的治療，從效果來看，兩人所患的埃博拉出血熱可以得到治愈.日本新研制的抗流感藥物法匹拉韋（Favipivir）也對埃博拉病毒病有一定的治療效果.2014年11月26日，美國國家衛(wèi)生研究院宣布，首個埃博拉疫苗cADV-EBOV成功通過臨床試驗.加拿大研制的VSV-EBOV疫苗也已經(jīng)開展人體臨床試驗.2014年8月，我國軍事醫(yī)學(xué)科學(xué)院生物流行病研究所歷時5年研制的對抗埃博拉病毒的藥物“jk-05”，通過總后衛(wèi)生部專家評審，獲得軍隊特需藥品批件.2014年9月，中國疾病預(yù)防控制中心病毒病所成功研制埃博拉病毒核酸、抗原和抗體檢測試劑.中國疾控中心派出的實驗室檢測隊攜帶了該檢測試劑，并利用該試劑在塞拉利昂開展病毒檢測任務(wù).

為了展示與埃博拉病毒研究相關(guān)的重要參考文獻、科技期刊、研究機構(gòu)、科研人員，系統(tǒng)全面地描述埃博拉病毒的來龍去脈，幫助研究人員更便捷地開展相關(guān)工作，特組織本專題.

本專題得到了高福院士（中國疾控中心副主任、中國科學(xué)院病原微生物與免疫學(xué)重點實驗室主任、中國科學(xué)院微生物研究所研究員）的大力支持.

·熱點數(shù)據(jù)排行·

截止2014年11月27日，中國知網(wǎng)（CNKI）和Web of Science的數(shù)據(jù)報告顯示，有關(guān)埃博拉病毒研究的期刊文獻分別為231與1373條，本刊將相關(guān)數(shù)據(jù)按照：機構(gòu)發(fā)文數(shù)、作者發(fā)文數(shù)、期刊發(fā)文數(shù)、被引用頻次進行排行，結(jié)果如下.

熱點追蹤

埃博拉病毒

·編者按·

2014年2月埃博拉病毒在幾內(nèi)亞境內(nèi)爆發(fā)，并先后波及利比里亞、塞拉利昂、尼日利亞、塞內(nèi)加爾、美國、西班牙、馬里等七國.埃博拉病毒是埃博拉病毒?。ㄔQ埃博拉出血熱）的病原體，在1976年中非地區(qū)暴發(fā)的疫情中首次被發(fā)現(xiàn).到目前為止，已確認的埃博拉病毒屬包括5個種，本次西非疫情的病原體為扎伊爾型埃博拉病毒，基因序列分析顯示，與既往疫情的扎伊爾型埃博拉病毒同源性為97%，存在一定的變異.根據(jù)世界衛(wèi)生組織公布的統(tǒng)計結(jié)果顯示，截止2014年11月15日，全球已有共計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發(fā)的感染及死亡人數(shù)都達到歷史最高.2014年11月10日，國際組織“無國界醫(yī)生”宣布，利比里亞感染埃博拉病毒的病例首次減少，但同時指出這并不意味著疫情結(jié)束.

目前，對抗埃博拉病毒的方法主要是注射NPC1阻礙劑，但是NPC1蛋白于細胞間進行運輸膽固醇，會阻擋膽固醇的運輸路線，造成尼曼匹克癥.治療性抗體（ZmappTM）的研究也在積極開展中，2名感染埃博拉病毒的美國醫(yī)護人員接受了實驗性藥物的治療，從效果來看，兩人所患的埃博拉出血熱可以得到治愈.日本新研制的抗流感藥物法匹拉韋（Favipivir）也對埃博拉病毒病有一定的治療效果.2014年11月26日，美國國家衛(wèi)生研究院宣布，首個埃博拉疫苗cADV-EBOV成功通過臨床試驗.加拿大研制的VSV-EBOV疫苗也已經(jīng)開展人體臨床試驗.2014年8月，我國軍事醫(yī)學(xué)科學(xué)院生物流行病研究所歷時5年研制的對抗埃博拉病毒的藥物“jk-05”，通過總后衛(wèi)生部專家評審，獲得軍隊特需藥品批件.2014年9月，中國疾病預(yù)防控制中心病毒病所成功研制埃博拉病毒核酸、抗原和抗體檢測試劑.中國疾控中心派出的實驗室檢測隊攜帶了該檢測試劑，并利用該試劑在塞拉利昂開展病毒檢測任務(wù).

為了展示與埃博拉病毒研究相關(guān)的重要參考文獻、科技期刊、研究機構(gòu)、科研人員，系統(tǒng)全面地描述埃博拉病毒的來龍去脈，幫助研究人員更便捷地開展相關(guān)工作，特組織本專題.

本專題得到了高福院士（中國疾控中心副主任、中國科學(xué)院病原微生物與免疫學(xué)重點實驗室主任、中國科學(xué)院微生物研究所研究員）的大力支持.

·熱點數(shù)據(jù)排行·

截止2014年11月27日，中國知網(wǎng)（CNKI）和Web of Science的數(shù)據(jù)報告顯示，有關(guān)埃博拉病毒研究的期刊文獻分別為231與1373條，本刊將相關(guān)數(shù)據(jù)按照：機構(gòu)發(fā)文數(shù)、作者發(fā)文數(shù)、期刊發(fā)文數(shù)、被引用頻次進行排行，結(jié)果如下.

國內(nèi)機構(gòu)發(fā)文數(shù)量排名 　　國外機構(gòu)發(fā)文數(shù)量排名

國內(nèi)期刊發(fā)文數(shù)量排名 　　國外期刊發(fā)文數(shù)量排名

根據(jù)中國知網(wǎng)（CNKI）數(shù)據(jù)報告，有關(guān)埃博拉病毒研究的高被引論文排行結(jié)果如下.

國內(nèi)數(shù)據(jù)庫高被引論文排行

根據(jù)Web of Science統(tǒng)計數(shù)據(jù)，有關(guān)埃博拉病毒研究的高被引論文排行結(jié)果如下.

國外數(shù)據(jù)庫高被引論文排行

（續(xù)表）

·高被引論文摘要·

被引頻次：10

埃博拉病毒的研究概況

楊濤

隨著研究的深入，埃博拉病毒逐漸被人類所認識.本文著重介紹了埃博拉病毒的一般特性、流行病學(xué)特性、埃博拉出血熱的發(fā)病機理、臨床表現(xiàn)和防治及其最新研究進展，對人們了解埃博拉病毒和開發(fā)抗埃博拉病毒的藥物與疫苗起到指導(dǎo)作用.

埃博拉病毒；埃博拉出血熱；病毒基因；絲狀病毒屬；自身免疫應(yīng)答；絲狀病毒科；病毒株；單股負鏈；自然宿主；表面蛋白

來源出版物：國際病毒學(xué)雜志， 2002， 9（5）: 152-155

被引頻次：9

抗埃博拉病毒VP40蛋白單克隆抗體的制備及在抗原捕捉ELISA中的應(yīng)用

王淑杰，王喜軍，胡森，等

摘要：本研究以原核表達、純化的扎伊爾株埃博拉病毒（Ebola virus， EBOV）VP40蛋白片段免疫BALB/c小鼠，通過雜交瘤技術(shù)制備單克隆抗體，獲得一株分泌抗EBOV VP40蛋白單克隆抗體的雜交瘤細胞系.以重組桿狀病毒表達EBOV VP40蛋白為抗原，經(jīng)Western blot和間接免疫熒光檢測該單克隆抗體顯示出良好的特異性免疫反應(yīng).采用該株雜交瘤細胞系經(jīng)腹腔注射接種8日齡BALB/c小鼠，制備腹水，并經(jīng)純化和HRP標(biāo)記，獲得HRP標(biāo)記的抗EBOV VP40蛋白單克隆抗體.從而，初步建立一種抗原捕捉ELSIA診斷方法，以原核表達EBOV VP40蛋白片段兔抗血清為一抗，應(yīng)用HRP標(biāo)記的抗EBOV VP40蛋白單克隆抗體檢測桿狀病毒表達的重組EBOV VP40蛋白顯示出良好的敏感性和特異性.結(jié)果表明，初步建立的抗原捕捉ELSIA診斷方法有希望成為一種理想的檢測EBOV感染的診斷方法.

關(guān)鍵詞：Ebola病毒；VP40蛋白；單克隆抗體

來源出版物：中國預(yù)防獸醫(yī)學(xué)報， 2008，30（4）: 309-313 聯(lián)系郵箱：王淑杰，zgb@hvri.ac.cn

被引頻次：7

埃博拉出血熱及埃博拉病毒的研究進展

許黎黎，張連峰

摘要：埃博拉病毒可以引起一種人畜共患烈性傳染病，即埃博拉出血熱，此病于1976年始發(fā)于埃博拉河流域，并且于該區(qū)域嚴重流行，故而得名.人類一旦感染埃博拉病毒，死亡率可高達88%，從而引起醫(yī)學(xué)界的廣泛關(guān)注，世界衛(wèi)生組織已將埃博拉病毒列為對人類危害最為嚴重的病毒之一.深入地了解埃博拉出血熱及埃博拉病毒，及其致病機理，對于埃博拉出血熱的預(yù)防和控制具有非常重要的意義.

關(guān)鍵詞：埃博拉出血熱；埃博拉病毒

來源出版物：中國比較醫(yī)學(xué)雜志， 2011， 21（1）: 70-74 聯(lián)系郵箱：張連峰，lianfeng_zhang3@yahoo.com.cn

被引頻次：436

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

被引頻次：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

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

被引頻次：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

來源出版物：Nature， 438（7068）: 575-576 聯(lián)系郵箱：Leroy， EM； eric.leroy@ird.fr

被引頻次：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

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

被引頻次：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

來源出版物：Science， 2005， 308（5728）: 1643-1645 聯(lián)系郵箱：Cunningham， JM； jcunningham@rics.bwh.harvard.edu

被引頻次：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

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

聯(lián)系郵箱：Kawaoka， Y； kawaokay@svm.vetmed.wisc.edu

被引頻次：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

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

被引頻次：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

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

被引頻次：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

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

被引頻次：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

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

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埃博拉病毒?。毫餍胁W(xué)、生態(tài)學(xué)、診斷、治療及控制

李昱，任翔，劉翟，等

摘要：埃博拉病毒（Ebolavirus）是埃博拉病毒?。‥bola Virus Disease，EVD）的病原體，1976年首次在非洲發(fā)現(xiàn)，目前確認該病毒包括5個種，其中蘇丹型（Sudan ebolavirus）、扎伊爾型（Zaire ebolavirus）、塔伊森林型（Ta Forest ebolavirus）和本迪布焦型（Bundibugyo ebolavirus）均有感染人發(fā)病的記錄；萊斯頓型（Reston ebolavirus）可致人隱性感染，并與多起獼猴暴發(fā)疫情有關(guān)，曾在菲律賓的豬中檢出.人類埃博拉病毒病的病死率為25%～90%，疫情均發(fā)生在非洲，主要集中在10°N—10°S的非洲地區(qū)，本次西非疫情是規(guī)模最大的暴發(fā)流行，截至2014年8月20日已報告2615例病例.該病是動物源性傳染病，目前證據(jù)支持果蝠可能為病毒的自然儲存宿主.該病在人群中主要通過接觸傳播，有癥狀的病人才具有傳染性.未采取正確防護措施的醫(yī)護人員、家庭護理人員及接觸病人血液、體液，或接觸病人血液、體液等污染的物品，或接觸病例尸體的人是高風(fēng)險感染人群.本病起病急，早期表現(xiàn)為發(fā)熱、厭食、虛弱無力等非特異性癥狀，可通過檢測病毒核酸、抗原、抗體等方法確診.目前尚無批準(zhǔn)上市的特效藥和疫苗，以對癥和支持治療為主.預(yù)防控制策略主要包括早期發(fā)現(xiàn)病例、及時調(diào)查處置、追蹤和密切觀察接觸者，以及有效的醫(yī)院內(nèi)和社區(qū)的感染控制.

關(guān)鍵詞：埃博拉病毒??；埃博拉病毒；流行病學(xué)

來源出版物：科技導(dǎo)報， 2014， 32（24）: 15-24 聯(lián)系郵箱：余宏杰，yuhj@chinacdc.cn

埃博拉病毒病：病原學(xué)、致病機制、治療與疫苗研究進展

程穎，劉軍，李昱，等

摘要：2013年12月始，埃博拉病毒病在幾內(nèi)亞、利比里亞、塞拉利昂和尼日利亞4國暴發(fā).其病原體——埃博拉病毒（Ebolavirus）于1976年被首次分離，為單股負鏈、不分節(jié)段、有囊膜的RNA病毒，屬絲狀病毒科，分5種，包括扎伊爾型、蘇丹型、本迪布焦型、塔伊森林型和萊斯頓型.其基因順序為3′端-NP-VP35-VP40-GP-VP30-VP24-L-5′端.埃博拉病毒屬于 A類病原，致病能力極強，操作活病毒需在生物安全4級實驗室進行.其主要靶細胞是血管內(nèi)皮細胞、肝細胞、巨噬細胞和樹突狀細胞等，通過抑制天然和獲得性免疫應(yīng)答反應(yīng)，增加血管通透性，引起肝臟等多臟器損傷，引發(fā)發(fā)熱、出血、多器官功能衰竭和休克等癥狀.目前尚無批準(zhǔn)上市的特異治療藥物和疫苗，處于研發(fā)或臨床試驗階段的治療藥物包括：（?。┛沽鞲胁《舅幬颰-705可能阻礙埃博拉病毒在細胞內(nèi)增殖，從而遏制感染；（ⅱ）ZMapp包含3種人源化的單克隆抗體，屬優(yōu)化的雞尾酒療法；（ⅲ）基于RNA干擾的基因治療藥物TKM-Ebola；（ⅳ）凝血調(diào)節(jié)因子、炎性介質(zhì)制劑，如源于絲蟲的抗凝蛋白 rNAPc2等.處于研發(fā)階段的疫苗有：（?。?fù)制缺陷型疫苗，安全性好，但誘導(dǎo)免疫的時間較長；（ⅱ）減毒復(fù)制型疫苗，效果好，但存在安全隱患.開展深入的病原學(xué)、免疫病理和致病機制研究，將有利于治療藥物和疫苗的研發(fā).同時，應(yīng)推進有希望的治療方案和疫苗進入人體臨床試驗階段.

關(guān)鍵詞：埃博拉病毒；基因組；免疫；致病機制；治療藥物；疫苗

來源出版物：科學(xué)通報， 2014， 59（30）: 2889-2989

雙重?zé)晒釸T-PCR檢測4種致病性亞型埃博拉病毒方法的建立

式中，bi是得分向量，它包含著不同樣本之間的信息關(guān)系，pi是加載向量，它包含著不同變量之間的信息關(guān)系，p是獨立變量的個數(shù)，G是剩余矩陣。

鐘玉清，鄭夔，蘇錦坤，等

摘要：目的 建立可同時檢測蘇丹、扎伊爾、本迪布焦和科特迪瓦4種致病性亞型埃博拉病毒的雙重?zé)晒釸T-PCR檢測方法.方法 根據(jù)4種致病性亞型埃博拉病毒的核蛋白NP基因保守序列，針對蘇丹型/扎伊爾型病毒以及針對本迪布焦型/科特迪瓦型病毒，相應(yīng)設(shè)計2套引物和探針.以體外轉(zhuǎn)錄的4種亞型埃博拉病毒 RNA為模板，進行條件的優(yōu)化以及方法特異性、靈敏度、重復(fù)性試驗，建立雙重?zé)晒釸T-PCR檢測方法.結(jié)果 新建立的雙重?zé)晒釸T-PCR方法檢測只對4種埃博拉病毒陽性對照RNA模板有特異性擴增，與腎綜合征出血熱病毒、登革病毒、黃熱病毒、西尼羅病毒、日本腦炎病毒、基孔肯雅病毒均無交叉反應(yīng)，2套引物和探針的檢測靈敏度均可達到最低50拷貝/μL.蘇丹型和本迪布焦型埃博拉病毒陽性對照RNA模板的4種稀釋度（2×108、2×106、2×104、2×102拷貝/μL）重復(fù)檢測3次均有較好的重復(fù)性.結(jié)論 建立的方法能同時檢測上述4種亞型埃博拉病毒，靈敏度高，特異性強，可用于埃博拉病毒疑似病例的檢測.

關(guān)鍵詞：埃博拉病毒；聚合酶鏈反應(yīng)

來源出版物：華南預(yù)防醫(yī)學(xué)， 2014， 40 （5）: 416-420

埃博拉病毒感染及其實驗室檢查

林迪，孫長貴

摘要：據(jù)世界衛(wèi)生組織官方報道，截至2014年8月4日埃博拉病毒累計感染1711人，并致932人死亡.埃博拉病毒是一種能引起人類和靈長類動物產(chǎn)生埃博拉出血熱的烈性傳染病病毒，該病毒致死率極高，為50%～90%.本文就該病毒的結(jié)構(gòu)、生物學(xué)特性、流行病學(xué)、臨床表現(xiàn)、診斷與鑒別診斷和實驗室檢查等作簡要綜述.

關(guān)鍵詞：埃博拉病毒；出血熱；流行病學(xué)；感染

來源出版物：試驗與檢驗醫(yī)學(xué)， 2014， 32（5）: 495-497

埃博拉病毒NP抗原表位區(qū)段的克隆和表達

王曉丹，李鵬飛，馮曉燕，等

摘要：目的 分析埃博拉病毒核蛋白（NP）抗原表位，克隆表達埃博拉病毒 NP抗原，為免疫學(xué)診斷試劑的研究奠定基礎(chǔ).方法 采用BioSun生物學(xué)軟件預(yù)測分析埃博拉病毒NP抗原的氨基酸表位區(qū)間，采用大腸桿菌優(yōu)勢密碼子反向翻譯成基因序列，采用PCR退火合成法合成NP優(yōu)勢密碼子抗原基因，并利用載體pBVIL1進行克隆表達.采用間接ELISA技術(shù)評價獲得NP抗原的特異性.結(jié)果 確定埃博拉病毒NP抗原的氨基酸表位位于360～739 aa，共設(shè)計36條引物，擴增合成1140 bp的NP抗原基因，克隆表達后，融合蛋白相對分子質(zhì)量為58×103，測序結(jié)果顯示插入的NP基因正確.初步結(jié)果顯示，NP抗原的特異性為99.24%（130/131）.結(jié)論獲得埃博拉病毒NP抗原，為進一步研制特異的埃博拉病毒快速診斷試劑提供了抗原儲備.

來源出版物：軍事醫(yī)學(xué)， 2014， 38（9）: 659-662

從《傷寒論》少陰病思考埃博拉出血熱辨治策略

劉清泉

摘要：世界衛(wèi)生組織日前宣布非洲埃博拉出血熱疫情為“國際關(guān)注的突發(fā)公共衛(wèi)生事件”，國家衛(wèi)生和計劃生育委員會發(fā)布了《埃博拉出血熱防控方案》.盡管目前中醫(yī)對埃博拉出血熱病沒有治療經(jīng)驗可談，但是在歷史上，中醫(yī)曾多次參與“出血熱”疫情的控制與治療，并獲得良效.從發(fā)病表現(xiàn)上，埃博拉出血熱符合《傷寒論》少陰病發(fā)病規(guī)律.埃博拉出血熱本次發(fā)病多為兩經(jīng)并病，故病重而亡多.據(jù)此目前初步分為四期：發(fā)病初期少陰太陽并病，吐利期少陰太陰并病，出血期少陰太陽蓄血并病，厥脫期少陰厥陰并病，臨床中應(yīng)嚴密觀察病情變化，觀其脈證，知犯何逆，主治從少陰，兼顧熱毒濕氣，隨證治之.

關(guān)鍵詞：埃博拉病毒；出血熱；傷寒論；少陰病

來源出版物：中醫(yī)雜志， 2014， 55 （18）: 1555-1557

西非埃博拉出血熱的五運六氣分析

顧植山

摘要：目的：探討中醫(yī)對當(dāng)前西非埃博拉疫情的治療方法.方法：從中醫(yī)的五運六氣和伏氣理論分析當(dāng)前西非埃博拉出血熱的病因病機、治法治則和遣方用藥特點.結(jié)果：當(dāng)前的西非埃博拉疫情與五運六氣及伏氣因素有關(guān)，其病機重點在伏寒傷陽；論治可以《傷寒論》少陰病篇有關(guān)條文為主要依據(jù)，宣發(fā)少陰伏邪，慎用清熱解毒重劑，亦可參考今年的三因司天運氣方附子山萸湯和正陽湯.結(jié)論：運氣失常是發(fā)生埃博拉疫情的重要原因，加強中醫(yī)運氣學(xué)說研究對西非埃博拉出血熱的防治具有重要意義.

關(guān)鍵詞：埃博拉病毒；疫情；西非；五運六氣

來源出版物：浙江中醫(yī)大學(xué)學(xué)報， 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

來源出版物：New England Journal of Medicine， 2014， 371（16）: 1481-1495 聯(lián)系郵箱：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

來源出版物：New England Journal of Medicine， 2014， 371（15）: 1418-1425 聯(lián)系郵箱：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

來源出版物：Nature， 2014， 514（7520）: 47-53 聯(lián)系郵箱：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

來源出版物：Science， 2014， 345（6202）: 1368-1372 聯(lián)系郵箱：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.

來源出版物：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.

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

（責(zé)任編輯 王帥帥，衛(wèi)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