Papillomaviruses infect cells via a clathrin-dependent pathway
Papillomaviruses infect cells via a clathrin-dependent pathway
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DOI：
10.1016/s0042-6822(02)00143-5
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发表时间：
2003-03-01
期刊：
影响因子：
3.7
通讯作者：
Schiller, JT
中科院分区：
文献类型：
--
作者：
Day, PM;Lowy, DR;Schiller, JT
在本研究中，我们以牛乳头瘤病毒(BPV)病毒粒子和小鼠C127细胞为模型系统，研究了乳头瘤病毒感染细胞的途径。在共聚焦显微镜下，BPV病毒粒子、BPV病毒样颗粒(VLP)和HPV16VLP的进入非常相似。在双重暴露的细胞中，HPV-16VLP和BPV病毒粒子共定位于细胞内。BPV VLP与AP-2、转铁蛋白受体、LAMP-2、LAMP-2、LAMP-2以及LAMP-2共定位。AP-2是一种网状蛋白适配分子，也是依赖网状蛋白的胞内途径的标志物。RT-PCR检测发现病毒粒子与细胞表面结合后12h内即可检测到BPV感染。感染可以通过几种药物抑制剂来预防，包括阻断依赖于笼蛋白的内吞作用的氯丙嗪和溶酶促进剂巴菲罗霉素A。相比之下，两种依赖小窝摄取的抑制剂非利平和制霉菌素不能防止BPV感染。我们得出结论，乳头瘤病毒通过依赖于笼蛋白的受体介导的内吞作用来感染细胞。令人惊讶的是，这种机制的内化动力学异常缓慢，BPV-1进入的t(1/2)大约为4h，而典型的配体为5-15min。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
In this study we have examined the pathway by which papillomaviruses infect cells, using bovine papillomavirus (BPV) virions and mouse C127 cells as the model system. By confocal microscopy, the entry of BPV virions, BPV virus-like particles (VLPs), and HPV16 VLPs were very similar. In dually exposed cells, HPV-16 VLPs and BPV virions colocalized intracellularly. BPV VLPs colocalized with AP-2, a clathrin adapter molecular and a marker of the clathrin-dependent endocytic pathway; and also with transferrin receptor, a marker of early endosomes; and Lamp-2, a marker of late endosomes and lysosomes. BPV infection was detected within 12 h of virion cell-surface binding, as measured by an RT-PCR assay. Infection was prevented by several pharmacologic inhibitors, including chlorpromazine, which blocks clathrin-dependent endocytosis and the lysosomotropic agent, bafilomycin A. By contrast, two inhibitors of caveolae-dependent uptake, filipin and nystatin, did not prevent BPV infection. We conclude that papillomaviruses infect cells via clathrin-dependent receptor-mediated endocytosis. Surprisingly, the kinetics of internalization were unusually slow for this mechanism, with the t(1/2) of entry of BPV-1 being approximately 4 h versus 5-15 min for a typical ligand. (C) 2003 Elsevier Science (USA). All rights reserved.