The ubiquitin-vacuolar protein sorting system is selectively required during entry of influenza virus into host cells
The ubiquitin-vacuolar protein sorting system is selectively required during entry of influenza virus into host cells
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DOI：
10.1046/j.1398-9219.2003.0140.x
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发表时间：
2003-12-01
期刊：
影响因子：
4.5
通讯作者：
Whittaker, GR
中科院分区：
文献类型：
--
作者：
Khor, R;McElroy, LJ;Whittaker, GR
流感病毒通过内吞作用进入细胞，并且需要晚期内体的低pH以成功感染。在这里，我们调查的要求，分选到多泡体途径的内吞作用。我们发现，用蛋白酶体抑制剂MG 132和lactacystin处理宿主细胞直接影响病毒复制的早期阶段。与其他病毒不同，如逆转录病毒，流感病毒的出芽不受影响。蛋白酶体功能的需求并不被其他两种pH依赖性病毒所共享：塞姆利基森林病毒和水泡性口炎病毒。使用MG 132处理，传入的流感病毒保留在与甘露糖6-磷酸受体部分共定位的核内体中，但不与早期或晚期核内体的经典标志物共定位。还观察到与Rme-1的共定位，这是内吞作用的再循环途径的一部分。此外，流感病毒进入依赖于空泡蛋白分选途径，因为显性阴性hVPS 4的过表达引起病毒在与hVPS 4蛋白部分共定位的内体样群体中的停滞。总体而言，我们得出结论，流感病毒选择性地需要泛素/空泡蛋白分选途径进入宿主细胞，它必须与特定的细胞机械细胞内分选在病毒感染的初始阶段。
Influenza virus enters cells by endocytosis, and requires the low pH of the late endosome for successful infection. Here, we investigated the requirements for sorting into the multivesicular body pathway of endocytosis. We show that treatment of host cells with the proteasome inhibitors MG132 and lactacystin directly affects the early stages of virus replication. Unlike other viruses, such as retroviruses, influenza virus budding was not affected. The requirement for proteasome function was not shared by two other pH-dependent viruses: Semliki Forest virus and vesicular stomatitis virus. With MG132 treatment, incoming influenza viruses were retained in endosomes that partially colocalized with mannose 6-phosphate receptor, but not with classical markers of early or late endosomes. Colocalization was also observed with Rme-1, which is part of the recycling pathway of endocytosis. In addition, influenza virus entry was dependent on the vacuolar protein sorting pathway, as over-expression of dominant-negative hVPS4 caused arrest of viruses in endosome-like populations that partially colocalized with the hVPS4 protein. Overall, we conclude that influenza virus selectively requires the ubiquitin/vacuolar protein sorting pathway for entry into host cells, and that it must communicate with a specific cellular machinery for intracellular sorting during the initial phase of virus infection.