Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Cell Host Microbe. 2009 Dec 17;6(6):523-35. doi: 10.1016/j.chom.2009.11.006.
Early in infection, adenovirus travels to the nucleus as a naked capsid using the microtubule motor cytoplasmic dynein. How the dynein complex is recruited to viral cargo remains unclear. We find that cytoplasmic dynein and its associated proteins dynactin and NudE/NudEL, but not LIS1 or ZW10, colocalized with incoming, postendosomal adenovirus particles. However, in contrast to physiological cargos, dynein binding to adenovirus was independent of these dynein-associated proteins. Dynein itself directly interacted through its intermediate and light intermediate chains with the adenovirus capsid subunit hexon in a pH-dependent manner. Expression of hexon or injection of anti-hexon antibody inhibited virus transport but not physiological dynein function. These results identify hexon as a direct receptor for cytoplasmic dynein and demonstrate that hexon recruits dynein for transport to the nucleus by a mechanism distinct from that for physiological dynein cargo.
在感染早期，腺病毒作为一种裸露的衣壳，利用微管动力蛋白细胞质动力蛋白进入细胞核。细胞质动力蛋白复合物如何被招募到病毒货物上仍不清楚。我们发现细胞质动力蛋白及其相关蛋白动力蛋白和 dynactin 以及 NudE/NudEL，但不是 LIS1 或 ZW10，与传入的、内体后的腺病毒颗粒共定位。然而，与生理货物相反，动力蛋白与腺病毒的结合不依赖于这些动力蛋白相关蛋白。动力蛋白本身通过其中间链和轻中间链与腺病毒衣壳亚基六邻体以 pH 依赖性方式直接相互作用。六邻体的表达或抗六邻体抗体的注射抑制了病毒的运输，但不抑制生理动力蛋白的功能。这些结果表明六邻体是细胞质动力蛋白的直接受体，并证明六邻体通过一种不同于生理动力蛋白货物的机制招募动力蛋白进行核运输。
