Imaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions.
Imaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions.
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作者：
人偏肺病毒（HMPV）可以通过病毒颗粒的出芽或直接细胞间传播在细胞间传播。在HMPV感染的细胞中形成出芽细丝和细胞间延伸的网络;然而，这些结构在感染的直接细胞间传播中的参与仍有待研究。利用先进的成像技术，我们表明，芽丝含有病毒RNA基因组，而不是反基因组，并成为丰富的HMPV F蛋白的感染进展。在其表面上含有F蛋白的多个细丝被观察到从一个细胞发出以接触相邻细胞，强烈地表明这些是出芽的丝状HMPV病毒粒子。此外，HMPV感染后，细胞间延伸的形态和性质的变化进行了检测。我们发现，细胞间的延伸允许转移的胞质染料只在HMPV感染的细胞。此外，使用实时成像，我们提供了新的证据，直接通过包涵体从细胞到细胞跨越细胞间的延伸。这些结果为HMPV的直接细胞间传播提供了新的见解，并表明这种传播模式可以通过不同的机制发生。人偏肺病毒是一种重要的呼吸道病原体，可导致显著的发病率和死亡率，特别是在非常年轻的人、老年人和免疫抑制者中。然而，这种病毒如何传播到新的靶细胞的分子细节尚不清楚。这项工作提供了关于与病毒颗粒一致的丝状结构形成的重要新信息，并为感染期间形成的细胞之间的延伸结构提供了重要的新见解。此外，它首次证明了病毒复制中心通过这些细胞间延伸的运动，代表了一种可能适用于其他病毒系统的直接细胞间传播的新模式。
Human metapneumovirus (HMPV) can spread between cells through budding of virus particles or direct cell-to-cell spread. A network of budding filaments and intercellular extensions forms in HMPV-infected cells; however, the involvement of these structures in direct cell-to-cell spread of infection remains to be investigated. Utilizing advanced imaging techniques, we show that budding filaments contain the viral RNA genome, and not the antigenome, and become enriched with HMPV F protein as infection progresses. Multiple filaments containing the F protein on their surface were seen emanating from one cell to contact a neighboring cell, strongly suggesting that these are budding filamentous HMPV virions. In addition, changes in the morphology and properties of intercellular extensions following HMPV infection were detected. We show that intercellular extensions allow the transfer of a cytosolic dye only in HMPV-infected cells. In addition, using live imaging, we provide novel evidence of the direct passage of inclusion bodies from cell-to-cell across intercellular extensions. These results provide novel insights into the direct cell-to-cell spread of HMPV and suggest that this mode of transmission can occur through different mechanisms. Human metapneumovirus is an important respiratory pathogen that causes significant morbidity and mortality, particularly in the very young, the elderly, and the immunosuppressed. However, the molecular details of how this virus spreads to new target cells are unclear. This work provides important new information on the formation of filamentous structures that are consistent with virus particles and adds critical new insight into the structure of extensions between cells that form during infection. In addition, it demonstrates for the first time the movement of viral replication centers through these intercellular extensions, representing a new mode of direct cell-to-cell spread that may be applicable to other viral systems.
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DOI：
10.1099/vir.0.2008/004051-0
发表时间：
2008-11
期刊：
The Journal of general virology
影响因子：
--
作者：
Derdowski A;Peters TR;Glover N;Qian R;Utley TJ;Burnett A;Williams JV;Spearman P;Crowe JE
通讯作者：
Crowe JE
影响因子：
3.7
作者：
NAKAI, T;SHAND, FL;HOWATSON, AF
通讯作者：
HOWATSON, AF
影响因子：
64.5
作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.
影响因子：
6.7
作者：
Martinez MG;Kielian M
通讯作者：
Kielian M
影响因子：
5.4
作者：
Guo, Rui;Katz, Benjamin B.;Fang, Ying
通讯作者：
Fang, Ying