Cryotomography of budding influenza A virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end.
Cryotomography of budding influenza A virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end.
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DOI：
10.1371/journal.ppat.1003413
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Bhella D
中科院分区：
文献类型：
--
作者：
Vijayakrishnan S;Loney C;Jackson D;Suphamungmee W;Rixon FJ;Bhella D
流感病毒在毒株之间的颗粒形态表现出显著的差异。甲型流感病毒的临床分离株已显示出产生长丝状颗粒，而实验室适应株主要是球形的。然而，丝状表型在流感病毒感染周期中的作用仍不确定。我们使用冷冻电子断层扫描进行第一个三维研究的丝状病毒超微结构的颗粒出芽从受感染的细胞。纤维通常长于10微米，有时在其前端有球根状的头部，其中一些包含我们归因于M1的小管，而没有可识别的核糖核蛋白（RNP），因此基因组片段。没有灯泡的长丝很少看到在其远端有一个有序的补充RNP。纯化病毒的成像也揭示了不同的丝状形态;短杆状病毒体和较长的丝状体。杆状病毒粒子含有RNP的有序补充，而较长的丝状颗粒较窄，大多数似乎缺乏这种特征，但通常沿其整个长度沿着含有纤维状物质。这些不同类别的颗粒之间的重要超微结构差异提高了感染过程中不同形态发生途径和功能的可能性。在实验室中培养的流感病毒通常产生球形颗粒。然而，从患者分离的病毒经常产生长的丝状颗粒，以及较小的椭圆形颗粒，我们称之为“杆状病毒体”。长纤维对于细胞间的传递可能是重要的，或者通过破坏呼吸道的粘液层来促进较小颗粒的释放。我们已经使用三维电子显微镜来研究流感病毒细丝从细胞中“出芽”的结构。我们发现许多长的花丝在离细胞最远的一端有一个大的球根状头部。这些球中的许多是空的，而一些包含小管，我们相信这些小管是由支架蛋白M1组成的，通常排列在病毒膜的内表面。杆状病毒体含有由八个RNA片段组成的基因组;这些片段各自包裹在蛋白质中并以有序的方式包装。球头花丝和极少数较窄的花丝都不具有这一特征。我们假设，我们所看到的不同的病毒结构表明不同的组装途径和功能。不包含基因组的长丝状结构可能会对抗免疫反应或帮助较小的病毒颗粒传播。
Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process. Influenza viruses that have been cultivated in the laboratory usually produce particles that are spherical. However, viruses isolated from patients frequently produce long filamentous particles, as well as smaller elliptical particles that we term “bacilliform virions”. Long filaments may be important for cell-to-cell transmission or facilitate release of the smaller particles by disrupting the mucous layer of the respiratory tract. We have used three-dimensional electron microscopy to investigate the structure of influenza virus filaments ‘budding’ from cells. We found that many of the long filaments had a large bulbous head at the end furthest from the cell. Many of these bulbs were empty while some contained tubules that we believe are made of a scaffold-protein M1 that usually lines the inner surface of the viral membrane. Bacilliform virions contain genomes comprised of eight segments of RNA; these are each wrapped up in protein and packaged in an ordered manner. None of the bulb-headed filaments and very few narrower ones had this feature. We hypothesise that the diverse viral structures we have seen suggest distinct assembly pathways and moreover functions. Long filamentous structures that do not appear to contain genomes may combat the immune response or help the smaller virus particles spread.
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DOI：
10.1126/science.1183173
发表时间：
2010-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Doceul V;Hollinshead M;van der Linden L;Smith GL
通讯作者：
Smith GL
DOI：
10.1073/pnas.73.9.3045
发表时间：
1976-01-01
影响因子：
11.1
作者：
MCGEOCH, D;FELLNER, P;NEWTON, C
通讯作者：
NEWTON, C
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
5.4
作者：
COMPANS, RW;CONTENT, J;DUESBERG, PH
通讯作者：
DUESBERG, PH
DOI：
10.1073/pnas.0437772100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Fujii, Y;Goto, H;Kawaoka, T
通讯作者：
Kawaoka, T