[转移贴]-PNAS:美国CDC在蝙蝠中发现新型A型流感病毒H17

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原帖由ipsvirus发表于8/3/2012 15:14

流感病毒分为甲（A）、乙（B）、丙（C）三型，甲型流感病毒最容易发生变异，世界上的几次流感大流行就是甲型流感病毒出现新亚型或旧亚型重现引起的。

甲型流感病毒根据H和N抗原不同，又分为许多亚型，H可分为16个亚型（H1～H16），N有9个亚型（N1～N9）。其中仅H1N1、H2N2、H3N2主要感染人类，其它许多亚型的自然宿主是多种禽类和动物。其中对禽类危害最大的为H5、H7和H9亚型毒株。一般情况下，禽流感病毒不会感染鸟类和猪以外的动物。但1997年香港首次报道发生18例H5N1人禽流感感染病例，其中6例死亡，引起全球广泛关注。1997年以后，世界上又先后几次发生了禽流感病毒感染人的事件。具有高致病性的H5N1、H7N7、H9N2、等禽流感病毒，一旦发生变异而具有人与人的传播能力，会导致人间禽流感流行，给人类带来致命的威胁。最近有实验室人为突变获得了这种可以在人与人之间传播的H5N1禽流感，在民众和科学界中都引起震动，吵的沸沸扬扬（可参考论坛帖子http://bbs.virology.com.cn/thread-28037-1-1.html  http://bbs.virology.com.cn/thread-28630-1-1.html  http://bbs.virology.com.cn/thread-28718-1-1.html  http://bbs.virology.com.cn/thread-29527-1-1.html  ）。

最近美国CDC在危地马拉（拉丁美洲国家）的一种蝙蝠身上发现了一种新型A型流感病毒。通过8条基因序列分析，此病毒不属于任何已发现的流感病毒亚型，命为H17型。研究人员在细胞和鸡胚中也不能传代培养，这也说明了这一新病毒的独特性。

尽管这是一种新型A型流感病毒，但研究人员认为它仍然可能会与已知病毒进行基因重排（reassortment），或可产生超级病毒，引起新流感大流行。

课题研究得到亚特兰大疾病控制和预防中心全球疾病监测项目资助。

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ipsvirus
A distinct lineage of influenza A virus from bats

Suxiang Tonga,1, Yan Lia, Pierre Rivaillerb, Christina Conrardya, Danilo A. Alvarez Castilloc, Li-Mei Chenb, Sergio Recuencod, James A. Ellisond, Charles T. Davisb, Ian A. Yorkb, Amy S. Turmelled, David Moranc, Shannon Rogersa, Mang Shia, Ying Taoa, Michael R. Weile, Kevin Tangf, Lori A. Rowef, Scott Sammonsf, Xiyan Xub, Michael Fracef, Kim A. Lindbladeg, Nancy J. Coxb, Larry J. Andersona, Charles E. Rupprechtd,1, and Ruben O. Donisb,1

Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses.

原文链接http://www.pnas.org/content/early/2012/02/17/1116200109

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ipsvirus
今年2月，一份发表于PNAS上的研究报告（见1楼）引起了社会广泛关注，研究人员从危地马拉3只果蝠体内检测出一种新型甲型流感病毒，从分类上看，该流感病毒完全不同于以往存在的流感病毒，属于一个新的亚型，研究人员把它定为H17N10亚型。

大家关心的问题是这种新型流感病毒会不会感染人，会不会在人群中传播并引发流感的暴发？种种疑虑和不安一时间笼罩在公众心头。高福课题组长期以来致力于流感病毒囊膜蛋白结构与病毒跨种间传播机制的研究。在第一时间内表达和纯化了该新型流感病毒神经氨酸酶（NA），对其结构和功能进行了详细的研究。该项研究成果近期发表在PNAS杂志上。

流感病毒神经氨酸酶（NA）是流感病毒表面最重要的糖蛋白之一，流感病毒通过血凝素蛋白(HA)与宿主细胞表面受体唾液酸结合侵入宿主细胞，然而，在病毒粒子释放时，HA与唾液酸的结合又成了病毒释放和迁移的障碍。NA在病毒侵染末期通过催化细胞表面糖蛋白分子上唾液酸从糖链上解离促进新生病毒颗粒的释放，帮助病毒粒子迁移，所以NA的活性与病毒的感染、传播与致病密切相关。

之前已发现的流感病毒NA有9个血清型（N1-N9），新发现的流感病毒NA属于第十个血清型（N10）。课题组研究人员利用昆虫细胞表达纯化的N10，检测了可溶性N10蛋白的神经氨酸酶活性，出乎预料的发现是N10没有传统NA所具有的神经氨酸酶活性，也就是说它不具备切割唾液酸的功能。从结构上看，N10与传统的NA相似，4个单体形成一个四聚体结构，在每个分子的表面都有一个类似于酶催化中心的区域。但是，进一步分析发现相比较其它NA，N10酶活性中心与酶活性相关的保守氨基酸有很多改变，致使酶活性中心构象发生了巨大变化，不利于底物唾液酸的结合。

这些发现暗示，新型蝙蝠流感病毒可能与以往的流感病毒有不同的侵染和释放机制，具有较严格的宿主特异性，在短时间内不会造成人际间传播。这为流感防控政策的制定提供了理论依据，同时，也为流感病毒的溯源、进化研究提供了新的思路。该项研究成果近期发表在PNAS杂志上。

http://www.bioon.com/biology/Immunology/530868.shtml

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Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus

Li Q, Sun X, Li Z, Liu Y, Vavricka CJ, Qi J, Gao GF.

The recent discovery of the unique genome of influenza virus H17N10 in bats raises considerable doubt about the origin and evolution of influenza A viruses. It also identifies a neuraminidase (NA)-like protein, N10, that is highly divergent from the nine other well-established serotypes of influenza A NA (N1-N9). The structural elucidation and functional characterization of influenza NAs have illustrated the complexity of NA structures, thus raising a key question as to whether N10 has a special structure and function. Here the crystal structure of N10, derived from influenza virus A/little yellow-shouldered bat/Guatemala/153/2009 (H17N10), was solved at a resolution of 2.20 ?. Overall, the structure of N10 was found to be similar to that of the other known influenza NA structures. In vitro enzymatic assays demonstrated that N10 lacks canonical NA activity. A detailed structural analysis revealed dramatic alterations of the conserved active site residues that are unfavorable for the binding and cleavage of terminally linked sialic acid receptors. Furthermore, an unusual 150-loop (residues 147-152) was observed to participate in the intermolecular polar interactions between adjacent N10 molecules of the N10 tetramer. Our study of influenza N10 provides insight into the structure and function of the sialidase superfamily and sheds light on the molecular mechanism of bat influenza virus infection.

原文链接http://www.pnas.org/content/early/2012/09/19/1211037109.long

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suenmomo

Proc Natl Acad Sci U S A. 2012 Oct 25. [Epub ahead of print]
The neuraminidase of bat influenza viruses is not a neuraminidase.
García-Sastre A.
Source
Department of Microbiology, Department of Medicine, Division of Infectious Diseases, and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029.

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deepblue
也有人持异议，包括一些美国院士。主要担心病毒没有成功拯救出来，缺少最关键的一条定论数据。再继续观察吧

rojjer

^_^
请教一个问题：除了唾液酸受体外，甲型流感病毒有没有其它的受体？