Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER
Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER
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DOI：
10.1038/35074539
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发表时间：
2001-05-01
影响因子：
21.3
通讯作者：
Helenius, A
中科院分区：
文献类型：
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作者：
Pelkmans, L;Kartenbeck, J;Helenius, A
猴病毒40（SV 40）是动物病毒中的一种特殊病毒，它通过小窝进入细胞，内化的病毒积聚在滑面内质网（ER）区室中。使用视频增强，双色，活荧光显微镜，我们显示了在CV-1细胞中的单个病毒颗粒的摄取。在与小窝结合后，SV 40以含有小窝蛋白-1的小泡离开质膜。然后，它进入较大的，周边细胞器与非酸性pH值。虽然富含小窝蛋白-1，这些细胞器不包含标记的内体，溶酶体，ER或高尔基体，也没有获得配体网格蛋白包被的囊泡内吞作用。在这些细胞器中几个小时后，SV 40被分选成管状的、无小窝蛋白的膜囊泡，这些膜囊泡沿着沿着微管快速移动，并沉积在核周的、突触融合蛋白17阳性的、光滑的ER细胞器中。微管破坏剂诺考达唑抑制这些管状载体的形成和运输，并阻断病毒感染。我们的研究结果表明，存在一个两步的运输途径，从质膜小窝，通过一个中间的细胞器（称为小窝），ER。该途径绕过内体和高尔基复合体，并且是SV 40使用的生产性感染途径的一部分。
Simian virus 40 (SV40) is unusual among animal Viruses in that it enters cells through caveolae, and the internalized virus accumulates in a smooth endoplasmic reticulum (ER) compartment. Using video-enhanced, dual-colour, live fluorescence microscopy, we show the uptake of individual virus particles in CV-1 cells. After associating with caveolae, SV40 leaves the plasma membrane in small, caveolin-1-containing vesicles. It then enters larger, peripheral organelles with a non-acidic pH. Although rich in caveolin-1, these organelles do not contain markers for endosomes, lysosomes, ER or Golgi, nor do they acquire ligands of clathrin-coated vesicle endocytosis. After several hours in these organelles, SV40 is sorted into tubular, caveolin-free membrane vesicles that move rapidly along microtubules, and is deposited in perinuclear, syntaxin 17-positive, smooth ER organelles. The microtubule-disrupting agent nocodazole inhibits formation and transport of these tubular carriers, and blocks viral infection. Our results demonstrate the existence of a two-step transport pathway from plasma-membrane caveolae, through an intermediate organelle (termed the caveosome), to the ER. This pathway bypasses endosomes and the Golgi complex, and is part of the productive infectious route used by SV40.