Three-Dimensional Organization of Rift Valley Fever Virus Revealed by Cryoelectron Tomography

Three-Dimensional Organization of Rift Valley Fever Virus Revealed by Cryoelectron Tomography
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DOI:
10.1128/jvi.01191-08
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发表时间:
2008-11-01
影响因子:
5.4
通讯作者:
Watowich, Stanley J.
Watowich, Stanley J.
中科院分区:
医学2区
文献类型:
--
作者:
Freiberg, Alexander N.;Sherman, Michael B.;Watowich, Stanley J.

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裂谷热病毒(RVFV)是布尼亚病毒科(猪属)病毒家族的成员,被认为是非洲最重要的病原体之一,可在牲畜和人类中引起病毒性人畜共患病。在这里,我们报告了RVFV疫苗株MP-12的三维结构组织的冷冻电子断层扫描表征。玻璃化水合病毒粒子呈球形,平均直径为100 nm。病毒糖蛋白形成圆柱形的中空尖状物,聚集成不同的囊泡。与以前关于RVFV是多形性的断言相反,RVFV MP-12的结构被发现是高度有序的。三维图谱的分辨率为6.1 nm,观察到病毒表面的囊粒呈二十面体晶格排列,具有明显的T=12准对称性。利用RVFV MP-12断层图像的傅立叶变换计算的自旋转函数中,所有二十面体对称轴都可见。据我们所知,以前只报道过乌库涅米病毒的三角测量数字为12,这是一种也属于白喉病毒属的布尼亚病毒。本研究的结果表明RVFV MP-12具有T=12的二十面体对称性,并提示白喉病毒属的其他成员以及布尼亚病毒科的成员也可能具有二十面体对称性。对病毒结构的了解可能为开发疫苗和诊断提供结构模板,因为没有有效的抗RVFV治疗方法可供人类使用。
Rift Valley fever virus (RVFV) is a member of the Bunyaviridae virus family ( genus Phlebovirus) and is considered to be one of the most important pathogens in Africa, causing viral zoonoses in livestock and humans. Here, we report the characterization of the three-dimensional structural organization of RVFV vaccine strain MP-12 by cryoelectron tomography. Vitrified-hydrated virions were found to be spherical, with an average diameter of 100 nm. The virus glycoproteins formed cylindrical hollow spikes that clustered into distinct capsomeres. In contrast to previous assertions that RVFV is pleomorphic, the structure of RVFV MP-12 was found to be highly ordered. The three-dimensional map was resolved to a resolution of 6.1 nm, and capsomeres were observed to be arranged on the virus surface in an icosahedral lattice with clear T = 12 quasisymmetry. All icosahedral symmetry axes were visible in self-rotation functions calculated using the Fourier transform of the RVFV MP-12 tomogram. To the best of our knowledge, a triangulation number of 12 had previously been reported only for Uukuniemi virus, a bunyavirus also within the Phlebovirus genus. The results presented in this study demonstrate that RVFV MP-12 possesses T = 12 icosahedral symmetry and suggest that other members of the Phlebovirus genus, as well as of the Bunyaviridae family, may adopt icosahedral symmetry. Knowledge of the virus architecture may provide a structural template to develop vaccines and diagnostics, since no effective anti-RVFV treatments are available for human use.