Limited Transferrin Receptor Clustering Allows Rapid Diffusion of Canine Parvovirus into Clathrin Endocytic Structures
Limited Transferrin Receptor Clustering Allows Rapid Diffusion of Canine Parvovirus into Clathrin Endocytic Structures
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DOI：
10.1128/jvi.07194-11
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发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Kirchhausen, Tom
中科院分区：
文献类型：
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作者：
Cureton, David K.;Harbison, Carole E.;Kirchhausen, Tom
病毒病原体篡夺细胞表面受体进入网格蛋白内吞结构，但这些结构的病毒纳入机制仍然不完全清楚。在这里，我们使用荧光显微镜直接可视化的协会与细胞转铁蛋白受体（TfR）的活猫细胞的表面上的单个犬细小病毒（CPV）衣壳，并监测这些CPV-TfR复合物访问内吞结构。我们发现，大多数衣壳与少于5个TfR和类似的TfR结合衣壳横向扩散到组装网格蛋白包被的坑小于30秒后附件的25%。没有遇到包被凹坑的衣壳从细胞表面解离，半衰期类似于30 s。总之，我们的研究结果显示CPV如何利用TfR内吞作用的天然机制来参与网格蛋白内吞途径，并揭示衣壳对猫TfR的低亲和力限制了衣壳在细胞表面上的停留时间，从而限制了病毒内化的效率。
Viral pathogens usurp cell surface receptors to access clathrin endocytic structures, yet the mechanisms of virus incorporation into these structures remain incompletely understood. Here we used fluorescence microscopy to directly visualize the association of single canine parvovirus (CPV) capsids with cellular transferrin receptors (TfR) on the surfaces of live feline cells and to monitor how these CPV-TfR complexes access endocytic structures. We found that most capsids associated with fewer than five TfRs and that similar to 25% of TfR-bound capsids laterally diffused into assembling clathrin-coated pits less than 30 s after attachment. Capsids that did not encounter a coated pit dissociated from the cell surface with a half-life of similar to 30 s. Together, our results show how CPV exploits the natural mechanism of TfR endocytosis to engage the clathrin endocytic pathway and reveal that the low affinity of capsids for feline TfRs limits the residence time of capsids on the cell surface and thus the efficiency of virus internalization.