我国科学家获得埃博拉病毒研究最新成果！

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    近日（2015年5月13日），国际顶尖学术期刊《自然》在线发表我国科学家关于埃博拉病毒最新研究成果：“Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone”，并同期配发评论文章”Latest Ebola data rule out rapid mutation”。

　　

    埃博拉病毒病以往被称作埃博拉出血热，因1976年第一次发现于埃博拉河附近的村庄而得名。埃博拉病毒具有强烈的致病性，其生物安全等级为4级（级数越大需要的防护措施越严格，艾滋病病毒与SARS病毒均为3级），在以往的疫情中病死率从25%到90%不等。2014年爆发于西非的埃博拉疫情是有史以来最大的一次疫情，已经造成超过2.5万人感染，超过一万人死亡；其中塞拉利昂当地超过3800人死亡。为积极配合国际援助西非埃博拉疫情防控，2014年9月，我国政府先后派出了以中国疾病预防控制中心、中国军事医学科学院、和中国医学科学院为主的中国援非抗埃医疗队移动检测队，在西非塞拉利昂持续工作10个多月，协同开展埃博拉疑似病例的检测与留观。

　　利用2014年7月至11月期间，在塞拉利昂的五个大区检测的3000多份埃博拉病人样本中，成功分离测定175株病毒全基因组序列。通过对于这些病毒基因组的系统分析，得到一系列重要的研究结论。首先，科研人员发现埃博拉病毒的进化速率相比于暴发初期明显降低，由每年每千个核苷酸位点2.03次突变减少为每年每千个核苷酸位点1.23次突变。之前以美国研究团队为主发表的研究成果提示埃博拉病毒突变速率远远高于历史数据，接近流感病毒的进化速率。这一结果引起了广泛的争论——进化速率的大幅提升将会给埃博拉疫苗和药物的研发造成巨大的影响。而此次最新数据和分析结果证实病毒的进化速率并未大幅提升，基本与历史平均速率相仿。推测之前的研究结果只是病毒特定进化时期的瞬时表现。

　　同时，最新的研究成果也表明，埃博拉病毒遗传多样性在持续增加，相比于之前的报道，中国科学家团队发现了440个单核苷酸多态性位点，其中有四分之一的位点是非同义突变位点，有可能造成病毒蛋白结构和性质的改变。研究结果提示这些位点在今后的研究工作中应该重点关注。此外，科学家还发现了可以用作病毒分型重要标记的病毒进化的差异性位点。通过病毒基因组比较分析，科学家还注意到了在6个病人体内的病毒存在串联突变的情况。这一发现在埃博拉病毒中首次被报道，关于其背后的生物学意义，还需要进一步的科学探索。

　　该项研究工作由国内几家优势单位合作完成，包括中国军事医学科学院、中国疾病预防控制中心、中国科学院、中国医学科学院，泰山医学院、华大基因研究院等。中国军事医学科学院微生物流行病学研究所所长曹务春，中国疾病预防控制中心副主任、中国科学院微生物研究所研究员、中国科学院院士高福，中国军事医学科学院院长、中国科学院院士贺福初为文章联合通讯作者。中国科学院微生物研究所刘翟研究员作为并列第一作者参与了埃博拉病毒的基因组分析和进化动力学研究。该研究受到中科院埃博拉研究专项、国家传染病重大专项、国家新药创制重大专项、科技部“863”微生物数字化信息系统集成关键技术研发，国家自然科学基金委创新研究群体等项目资助。

　　文章链接：

　　http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14490.html

　　同期评论链接：

　　http://www.nature.com/news/latest-ebola-data-rule-out-rapid-mutation-1.17554

　　图一，埃博拉病毒采集分布、传播路线和进化动力学。a,埃博拉病毒样本采集与测序区域；b,埃博拉病毒在塞拉利昂的潜在传播路径；c,2014年埃博拉病毒的进化速率；d,埃博拉病毒有效种群增长趋势。

　　图二，埃博拉病毒的基因组变异与基因多态性

Nature评论原文：

The Ebola virus evolved as it spread through West Africa last year — but its mutation rate did not accelerate, as some had thought, according to an analysis of genetic sequence data published on 13 May in Nature1. The data offer reassurance that the scope of the current epidemic did not make it possible for the virus to evolve into a more virulent or deadlier form.

The virus's evolution rate during the current epidemic, and whether it is changing in ways that make it easier to transmit, or more or less lethal, has been hotly debated. To address these questions, a team led by Wu-Chun Cao, an epidemiologist at the State Key Laboratory of Pathogen and Biosecurity in Beijing, sequenced 175 Ebola virus genomes from people who were infected with the virus, including some who died.

Nature special: Ebola outbreak

The samples were collected between 28 September and 11 November 2014 by the China Mobile Laboratory Testing Team, a diagnostic lab deployed by the Chinese government. Cao’s group combined the sequencing data from these specimens with sequences published in August by Pardis Sabeti, a computational geneticist at the Broad Institute in Cambridge, Massachusetts, and her colleagues2. Sabeti's study examined virus samples collected from patients in May and June. The combined data allowed Cao and his colleagues to track how the Ebola virus changed as it spread east to west across Sierra Leone. Ebola entered the country in May and reached the capital city, Freetown, in July.

Separate evolutions

The analysis finds that the virus evolved as it spread to new areas. But it did not change at a faster rate than it has in past outbreaks — even though those outbreaks were localized to much smaller areas and infected fewer people. And there is no evidence that Ebola evolved harmful mutations as it spread through Sierra Leone. “This is just the virus doing what it does,” says David Robertson, a computational and evolutionary biologist at the University of Manchester, UK.

Cao’s team reports that the virus continued to evolve more diversity as it spread, meaning that the viruses involved in each localized outbreak evolved independently of each other. “As the epidemic spread, it created many chains of infections, each of which was mutating in a different direction,” says viral geneticist Trevor Bedford at the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Cao’s team catalogued a total of 440 new mutations, and found that changes occurred most often in Ebola's glycoprotein gene, which encodes instructions for the surface protein that helps the virus attach to human cells. This could mean that human immune response was driving the virus's evolution, or it could be down to chance. “It’s surprisingly difficult to gauge functional change from sequence data alone,” Bedford says.

Virus function

Other researchers continue to examine such shifts as more data come out; for instance, Robertson has noted that in Sabeti’s data, many of the genetic changes that could potentially alter the virus's function occurred in regions that are more likely to affect how the virus interacts with human cells3. “It would be interesting to see if this is still the case” in the latest data, Robertson says.

The paper by Cao and colleagues greatly increases the publicly available data on Ebola viruses, but there is still a paucity of sequence data from Guinea and Liberia. That appears to be changing, however: a consortium led by Public Health England has released sequencing data on 179 Ebola samples collected in Guinea by the European Mobile Laboratory consortium.