Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids.
Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids.
复制标题
冷冻EM分析揭示了真正的鼠乳头瘤病毒衣壳的固有灵活性。
DOI：
10.3390/v13102023
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发表时间：
2021-10-07
期刊：
影响因子：
--
通讯作者：
Hafenstein SL
中科院分区：
文献类型：
--
作者：
Hartmann SR;Goetschius DJ;Hu J;Graff JJ;Bator CM;Christensen ND;Hafenstein SL
人乳头瘤病毒（HPV）是一种重要的健康负担，也是病毒引起的癌症的主要原因。然而，由于限制性嗜性使得高滴度病毒的生产和纯化成问题，研究受到阻碍。这个问题已经通过开发替代的HPV生产方法如病毒样颗粒（VLP）而克服，其缺乏天然病毒基因组。由于VLP衣壳的异质性、脆弱性和稳定性，结构研究的分辨率有限。这里提出的小鼠乳头瘤病毒（MmuPV1）提供了一个机会，在一个共同的实验室动物的背景下，研究一种天然的乳头瘤病毒。使用cryo EM来解决MmuPV1的结构，我们用局部对称细化方法实现了3.3 μ m的分辨率，该方法定义了更小的对称相关亚粒子。由此产生的高分辨率结构使我们能够首次构建MmuPV1不对称单元并识别推定的L2密度。我们还使用我们的程序ISECC来量化衣壳柔性，这表明衣壳作为由柔性接头连接的刚性体移动。MmuPV1的灵活性与以前表征的HPV VLP的灵活性相当。由此产生的MmuPV1结构是乳头瘤病毒研究中有希望的一步，并将为继续进行乳头瘤病毒的生物化学，遗传学和生物物理学研究提供框架。
Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. However, studies have been hampered due to restricted tropism that makes production and purification of high titer virus problematic. This issue has been overcome by developing alternative HPV production methods such as virus-like particles (VLPs), which are devoid of a native viral genome. Structural studies have been limited in resolution due to the heterogeneity, fragility, and stability of the VLP capsids. The mouse papillomavirus (MmuPV1) presented here has provided the opportunity to study a native papillomavirus in the context of a common laboratory animal. Using cryo EM to solve the structure of MmuPV1, we achieved 3.3 Å resolution with a local symmetry refinement method that defined smaller, symmetry related subparticles. The resulting high-resolution structure allowed us to build the MmuPV1 asymmetric unit for the first time and identify putative L2 density. We also used our program ISECC to quantify capsid flexibility, which revealed that capsomers move as rigid bodies connected by flexible linkers. The MmuPV1 flexibility was comparable to that of a HPV VLP previously characterized. The resulting MmuPV1 structure is a promising step forward in the study of papillomavirus and will provide a framework for continuing biochemical, genetic, and biophysical research for papillomaviruses.
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影响因子：
3.7
作者：
Clarke MA;Rodriguez AC;Gage JC;Herrero R;Hildesheim A;Wacholder S;Burk R;Schiffman M
通讯作者：
Schiffman M
影响因子：
3.7
作者：
Guan J;Bywaters SM;Brendle SA;Lee H;Ashley RE;Makhov AM;Conway JF;Christensen ND;Hafenstein S
通讯作者：
Hafenstein S
影响因子：
3.4
作者：
BAKER, TS;NEWCOMB, WW;BROWN, JC
通讯作者：
BROWN, JC
影响因子：
13.2
作者：
Cladel, Nancy M.;Jiang, Pengfei;Hu, Jiafen
通讯作者：
Hu, Jiafen
影响因子：
5.4
作者：
He, Maozhou;Chi, Xin;Xia, Ningsha
通讯作者：
Xia, Ningsha