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The author:(作者)delvpublished in(发表于) 2014/1/10 8:21:29 Chinese Academy of Sciences expert： H7N9 virus has limited interpersonal communication skills
H7N9: mutations, there are risks
Institute of Microbiology, has cracked the most alarming both avian influenza virus H5N1 and H7N9 cross-species communication mechanisms and H7N9 virus has suddenly discovered, starting with limited interpersonal communication abilities.
Reporter _ Beijing Shi Yue Xu Xiaoxi intern _ Du Xue
Both government officials, scientists and the general public, can't wait to figure out two issues, bird flu will person-to-person? When person-to-person transmission of avian influenza?
H5N1 and H7N9 are two avian influenza virus to humans most at risk in recent years, after the H5N1 virus in infected humans for the first time since 1997, and in more than 60 countries worldwide, the mortality rate as high as 60%. H7N9 in late February 2013 first appeared in China's Yangtze River Delta region, and was menacing, in 10 months, China's 12 provinces found 148 people, including 46 deaths.
In such a rush, Vice President of the Institute for biological science, Chinese Academy of Sciences Beijing, Institute of Microbiology researcher, Deputy Director of the Chinese Center for disease control and prevention, George f. Gao, led his team, from the molecular level, broke the current two most worrisome mechanism of avian influenza virus H5N1 and H7N9 cross-species transmission.
Looking for key mutations
Associate research fellow, Institute of Microbiology, Liu Zhai had, for example, a flu virus's eight genes form a team in which coded HA (hemagglutinin) was captain to help viruses enter cells; codes NA (neuraminidase enzyme) was vice captain, responsible for the release of virus from cell; the other six internal gene segments responsible for virus replication.
George f. GAO study team primarily concerned with HA protein, that is, viruses from infecting cells in the keys, it can with cell surface receptors to help viruses opened cell doors, this correspondence as a lock and key.
Influenza virus is not a panacea, it cannot enter the cells of all species, which have their own preferences with cell receptors, some flu virus only in conjunction with the chicken cells, some influenza virus can invade human cells.
Exists in the human upper respiratory tract of sialic acid receptor α -2,6 glycosidic linkage connection, traditional seasonal human influenza viruses are very good at identifying and combining this receptor, which invade human cells. Also exists in the lower respiratory tract and respiratory tract of poultry is similar to α- -2,3 receptors, this is avian influenza viruses like the combination of receptors.
Typically, lower respiratory tract of avian influenza virus is not easy to reach out to people, and only when the virus reaches a certain number, will it be possible to reach the lower respiratory tract, causing severe pulmonary infection, which is also low incidence of avian influenza virus, and the only reason death rates are so high.
Although H7N9 and has not yet received widespread person-to-person transmission of H5N1 virus, and once the disease through genetic mutation or distribution, ability to obtain preference combined with human upper respiratory tract cells, spreads are likely to have evolved from avian influenza viruses.
Governments, scientists and the public has been worrying, such a situation ever arise? After all, historically, due to gene mutation and won the transmissibility of reassortant influenza H1, H2 and H3, has been extensively popular in the crowd, there was "great influenza".
The case of H5N1, George f. Gao and his research team in May 2013, a paper published in the journal Science found that the highly lethal strain in the event of Q226L amino acid mutations, you would be binding and human respiratory cells. Q226L amino acid mutations has long been widely followed, it is H2, H3 subtype influenza history, cause of avian influenza into a human influenza pandemic.
H5N1 is also dire in, it happened once the mutation will not only won the ability to combine with human upper respiratory tract, and also changed its preference, it becomes easy to infect human cells, which means that the it person to person.
"The current monitoring of natural mutations of the H5N1 virus this terrible, but there is research evidence that H5N1 virus mutates and becomes more easily infect humans. "The paper's lead author, Deputy researcher of the Chinese Academy of Sciences Institute of biological sciences, Beijing, Shi Yi said.
It is regrettable that, in current scientific level, humans can't predict what time will mutate, led to this very high mortality rate of the virus can be transmitted from person.
Soon, George f. Gao team also has a new research findings H7N9: on September 5, 2013 papers published in the journal Science said H7N9 circulating virus strains is already in four key mutation of amino acids, ability to obtain binding and human respiratory cells.
However, H7N9 is essentially an avian influenza virus, because it prefers to poultry and have the same binding receptors in lower respiratory tract cells. This means that H7N9 can invade on human respiratory cells, but only have limited transmission capacity, namely "limited person-to-person transmission."
"Invasion of lower respiratory tract virus likes to stay in the lungs, the virus in the lungs to be exhaled, it is more difficult, there are many mucus trap, making it unable to effectively spread," said Shi Yi. "The viruses that are widely circulated in the crowd, it must be the preferred binding of α- -2,6 receptor, which is more easily combined with upper respiratory tract cells, breathed easier and easier to spread. "
Currently, George f. Gao of the research teams are looking for variations that might lead to preference and H7N9 viruses combined, "now there are a number of directions, whether H7N9 or H5N1, once preference and combined virus, very likely to blame for the next pandemic," Shi warned.
"Magic box"
Meanwhile, Liu Zhai, who is also using bioinformatics methods in an attempt to find out how avian influenza and wild birds-gene reassortant, and spread by poultry transport. According to their study, H7 entered Chinese poultry from wild birds already has a history, H7N3 in some provinces early distributions. N9 seldom found in China before and presumed incoming from migratory birds, most likely through wild geese and ducks and waterfowl into poultry. Due to the lack of sampling, a belief that there is currently a lack of conclusive evidence.
From April 2013, H7N9 in Shanghai as the Center, to spread around a circle, each to a new area, H7N9 with local chicken H9N2 virus reassortant in replacement of internal genes, known as "recruit players from the local". H9N2 because of its widely distributed in China and variety of numerous and H7N9 in quickly to produce new and different genotypes. By genotype data, one is able to infer the avian flu spread through poultry transport path, combined with the realities, you can cross-regional monitoring to provide early warning for the transport of live poultry.
"We are through cross-species communication mechanism and study on propagation path, and provide some recommendations to decision makers, for example, we developed this amino acid mutations is important, can result in person-to-person, then you're monitoring if such a mutation occurs in the natural world, as soon as this mutation, to improve prevention and control. "George f. GAO said.
Starting from 2005 in Qinghai Lake, George f. GAO study on bird flu has entered for ten years, he himself has recently elected academician. Recently, he also hosted on CCTV's 2013 celebration of science and technology was awarded the annual sci-tech innovation on people, selected on the grounds that "H7N9 virus and new flu outbreak prevention and control strategy provides an important theoretical foundation. "
George f. Gao, closing live bird markets, intensive culture, centralized slaughter and culled diseased birds is the best way. But under complicated conditions in China, the best policy would not necessarily be used. H7N9 after the outbreak, Shanghai was closed for a short time the live bird markets, and subsequently reopened, "Chinese people are used to eating live poultry, that cultural practices could not be changed overnight, can all take, take time. "
Currently for H5N1 virus, China of control measures is on poultry injection vaccine, also is has controversy of a items control measures, "in vaccine of pressure Xia, virus also may occurred mutations, most ideal of State also is culled, but consider to culled of economic cost, vaccine is complex situation Xia of a helpless select," George f. GAO said, "we not knows," Pandora "magic box what when will was open, inside will fly out what, we can do of, is in it open zhihou, as soon as possible cover Shang it. " Source: to be sexy
H7N9：已突变，有风险
中科院微生物所已破译了目前最让人担忧的两种禽流感病毒H5N1和H7N9 跨种传播机制，并发现H7N9病毒已经出现突变，开始具备有限的人际传播的能力。
记者_石悦 徐小西 北京报道 实习记者_杜雪
无论是政府官员、科学家还是普罗大众，都迫不及待地想弄清楚两个问题，禽流感会不会人传人？禽流感什么时候会人传人？
H5N1和H7N9是近年来对人类威胁最大的两种禽流感病毒，H5N1病毒自1997年在首次感染人类后，在全球60多个国家肆虐，死亡率高达60%。H7N9在2013年2月底在中国长三角地区首次出现后，也是来势汹汹，在10个月内，中国12个省市发现了148人感染 ，其中46人死亡。
在这样的尖峰时刻，中国科学院北京生命科学研究院副院长、微生物研究所研究员、中国疾病预防控制中心副主任高福，带领他的研究团队，从分子水平上，破译了目前最让人担忧的两种禽流感病毒H5N1和H7N9 跨种传播机制。
寻找关键突变
中科院微生物所副研究员刘翟打了个比方，一个流感病毒中的八个基因构成了一个团队，其中编码HA(血凝素)的是队长，帮助病毒进入细胞；编码NA(神经氨酸酶)的是副队长，负责病毒从细胞的释放；其他六个内部基因片段主要负责病毒的复制。
高福的研究小组主要关注HA蛋白，也就是病毒入侵细胞的钥匙，它能够跟细胞表面的受体结合，帮助病毒打开细胞的大门，这种对应关系如同钥匙和锁。
流感病毒不是万能的，它不能进入所有物种的细胞，它有各自偏好结合的细胞受体，有的流感病毒只能结合鸡的细胞，有的流感病毒则能入侵人类细胞。
人的上呼吸道中存在着α-2,6糖苷键连接的唾液酸受体，传统的季节性人类流感病毒非常善于识别并结合这种受体，进而入侵人类的细胞。而下呼吸道中则同时存在与家禽的呼吸道类似的α-2,3型受体，这正是禽流感病毒喜欢结合的受体。
通常情况下，禽流感病毒不容易深入到人的下呼吸道，而只有当病毒达到一定数量时，才有可能到达下呼吸道，引起严重的肺部感染，这也是禽流感病毒发病率低，而致死率如此之高的原因。
虽然H7N9和H5N1病毒尚未获得广泛的人传人能力，而病毒一旦通过基因突变或者重配，获得了偏好结合人体上呼吸道细胞的能力，就很可能会进化出能在人际传播的禽流感病毒。
各国政府、科学家和公众一直在担忧，这种情况究竟会不会出现？毕竟在历史上，由于基因突变和重配而获得了人际传播能力的H1、H2和H3型流感，都在人群中有过大范围的流行，还出现过"大流感"。
以H5N1为例，高福和他的研究团队在2013年5月发表在《科学》杂志的一篇论文就发现，这种致死率极高的病毒，一旦发生Q226L的氨基酸突变，就会获得和人类上呼吸道细胞结合的能力。Q226L氨基酸突变早已广受关注，这正是历史上H2、H3型流感，由禽流感变成了人流感的原因。
H5N1的可怕之处还在于，它一旦发生了突变，不但会获得了与人类上呼吸道结合的能力，它的偏好性也会随之发生改变，变得容易感染人类细胞，这就意味着，它能够人传人。
"好在目前监测的天然H5N1病毒还没有发生这种可怕的突变，但也有研究表明H5N1病毒正在发生变异，变得更容易感染人类。" 论文的第一作者，中科院北京生命科学研究院副研究员施一说。
遗憾的是，在现有科学水平上，人类无法预测在什么时间会发生变异，导致这种死亡率极高的病毒可以人传人。
很快，高福团队对H7N9的研究也有了新发现：他们在2013年9月5日在《科学》杂志上发表论文称，H7N9的某些流行病毒株已经在四个关键的氨基酸位点发生突变，获得了和人类上呼吸道细胞结合的能力。
但是，H7N9本质上还是一种禽流感病毒，因为它更喜欢与拥有和家禽一样的受体的下呼吸道细胞结合。这意味着，H7N9虽然能入侵人类上呼吸道细胞，但只具备了有限的人际传播能力，也即"有限的人传人"。
"入侵下呼吸道的禽流感病毒喜欢呆在肺部，肺部里的病毒要被呼出，是比较困难的，有很多黏液把它束缚住，让它无法有效传播，"施一说。"要想在人群中广泛传播的病毒，它必须是偏好性结合α-2,6型受体，也就是更容易与上呼吸道细胞结合，呼进呼出更容易，更易于被传播。"
目前，高福的研究团队正在寻找可能导致H7N9病毒偏好与人结合的变异，"目前已经有了一些方向，不管H7N9还是H5N1，一旦变成偏好与人结合的病毒，极有可能成为下一个大流感的罪魁祸首，"施一警告。
"魔盒"仍在
另一方面，刘翟等人也在用生物信息学的方法，试图摸清禽流感是如何与野鸟的基因重配，又是如何通过家禽的运输来传播的。根据他们的研究，H7从野鸟进入中国的家禽已经有一段历史，H7N3在一些省份早有分布。而N9之前在中国很少发现，据推测是从迁徙鸟类中传入，很可能是通过雁鸭类水禽进入家禽的。由于采样缺失，这个观点目前缺乏确凿证据。
自2013年4月以来，H7N9以上海为中心，一圈圈向周围传播，每到一个新的地区，H7N9都与当地鸡群中的H9N2病毒发生重配更换内部基因，也就是"从当地招募队员"。由于H9N2本身在中国分布广泛且变种众多，H7N9也在迅速地产生不同的新基因型。通过基因型分子数据，人们能够推断出禽流感通过家禽运输的传播路径，再与现实情况相结合，就可以为跨地区活禽运输的监测提供预警。
"我们就是通过跨种传播机制和传播路径的研究，给决策提供一些建议，比如说我们研究出来这个氨基酸突变很重要，会导致人传人，那你就监测自然界会不会出现这种突变，一旦出现这种突变，就要提高防控。"高福说。
从2005年的青海湖开始，高福的禽流感研究已经进入了十个年头，他本人最近也当选了中科院院士。最近，他还在中央电视台主办的2013年科技盛典上被评为年度科技创新人物，入选理由是"为H7N9病毒和新型流感暴发的防控策略提供了重要的理论基础。"
在高福看来，关闭活禽市场、集约化养殖、集中宰杀和扑杀病禽是上策。但在中国的复杂情况下，上策不一定会被采用。H7N9疫情暴发之后，上海曾经短时间关闭了活禽市场，随后又重新开放，"中国人吃惯了活禽，这种文化习惯不可能一下子改变，可以慢慢来，需要时间。"
目前对于H5N1病毒，中国的防控措施是对家禽注射疫苗，同样是有争议的一项防控措施，"在疫苗的压力下，病毒也可能发生突变，最理想的状态还是扑杀，但考虑到扑杀的经济代价，疫苗是复杂形势下的一种无奈选择，"高福说，"我们不知道，"潘多拉"魔盒什么时候会被打开，里面会飞出什么，我们能做的，就是在它打开之后，尽快盖上它。"来源：南都周刊
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