Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein.
Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein.
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DOI：
10.1007/s00401-010-0644-7
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发表时间：
2010-05
影响因子：
12.7
通讯作者：
Plattet P
中科院分区：
文献类型：
--
作者：
Wyss-Fluehmann G;Zurbriggen A;Vandevelde M;Plattet P
犬瘟热病毒（CDV）感染中，病毒持续存在的机制，即炎症性脱髓鞘慢性进展背后的驱动力，与非溶细胞性病毒细胞间传播有关。在这里，我们研究了表达重组荧光蛋白的强毒CDV在原代犬星形胶质细胞中传播的分子机制。延时视频显微镜记录了CDV传播是非常有效的利用细胞过程接触远程靶细胞。引人注目的是，CDV可以在不到6小时的时间内传播到远处的细胞，这表明CDV在胶质细胞中传播并不需要一个完整的病毒周期，并产生细胞外自由颗粒。滴定实验和电子显微镜证实，尽管膜相关病毒滴度较高，但CDV颗粒的产生非常低。有趣的是，共聚焦激光显微镜和慢病毒转导显示了病毒融合机制的表达和功能，包括病毒融合(F)和附着(H)糖蛋白，在细胞表面。重要的是，使用单周期感染性重组H敲除，H补充病毒，我们证明了H，从而潜在的病毒融合复合体，是使CDV传播所必需的。此外，由于我们无法在脑细胞中检测到CD150/SLAM的表达，因此我们认为存在一种尚未鉴定的CDV胶质受体。总之，我们的研究结果表明，CDV感染的持久性是由于需要CDV- h蛋白的细胞内细胞间传播。病毒转移，选择性地发生在星形胶质细胞过程的尖端，可能有助于病毒在星形胶质网络中覆盖很长的距离，在脱髓鞘斑块中“逃脱”宿主的免疫反应，从而不断引发新的病变。
The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, “outrunning” the host’s immune response in demyelinating plaques, thus continuously eliciting new lesions.
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影响因子：
3.7
作者：
Brettschneider J;Tumani H;Kiechle U;Muche R;Richards G;Lehmensiek V;Ludolph AC;Otto M
通讯作者：
Otto M
影响因子：
3.8
作者：
Moll, M;Pfeuffer, J;Maisner, A
通讯作者：
Maisner, A
影响因子：
3.7
作者：
Rivals, Jean-Paul;Plattet, Philippe;Wittek, Riccardo
通讯作者：
Wittek, Riccardo
影响因子：
5.4
作者：
Ehrengruber, MU;Ehler, E;Naim, HY
通讯作者：
Naim, HY
影响因子：
5.4
作者：
Duprex, WP;McQuaid, S;Rima, BK
通讯作者：
Rima, BK