Role of Protein Kinase C βII in Influenza Virus Entry via Late Endosomes
Role of Protein Kinase C βII in Influenza Virus Entry via Late Endosomes
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DOI：
10.1128/jvi.77.1.460-469.2003
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发表时间：
2003-01
影响因子：
5.4
通讯作者：
S. Sieczkarski;H. Brown;G. Whittaker
中科院分区：
文献类型：
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作者：
S. Sieczkarski;H. Brown;G. Whittaker
摘要 许多病毒利用受体介导的内吞作用来进入靶细胞。我们利用流感病毒和塞姆利基森林病毒 (SFV) 来定义蛋白激酶 C βII (PKCβII) 在内吞运输中的作用。我们发现特定的 PKC 抑制剂可以预防流感病毒感染，这表明 PKC 的经典亚型具有一定的作用。我们还检查了病毒进入过度表达显性阴性形式 PKCα 和 -β 的细胞。表达磷酸化缺陷形式的 PKCβII (T500V) 的细胞，但不表达等效的 PKCα 突变形式，抑制流感病毒成功进入——病毒在晚期内体中积聚。然而，SFV 据信从早期内体进入细胞，不受 PKCβII T500V 表达的影响。我们还检查了两种细胞配体、转铁蛋白和表皮生长因子（EGF）的运输。 PKCβII T500V 表达特异性阻断 EGF 受体运输和降解，而不影响转铁蛋白受体回收。与流感病毒一样，在 PKCβII 激酶死亡细胞中，EGF 受体被捕获在晚期内体区室中。我们的研究结果表明 PKCβII 是流感病毒进入和感染所需的晚期内体分选事件的重要调节因子。
ABSTRACT Many viruses take advantage of receptor-mediated endocytosis in order to enter target cells. We have utilized influenza virus and Semliki Forest virus (SFV) to define a role for protein kinase C βII (PKCβII) in endocytic trafficking. We show that specific PKC inhibitors prevent influenza virus infection, suggesting a role for classical isoforms of PKC. We also examined virus entry in cells overexpressing dominant-negative forms of PKCα and -β. Cells expressing a phosphorylation-deficient form of PKCβII (T500V), but not an equivalent mutant form of PKCα, inhibited successful influenza virus entry—with the virus accumulating in late endosomes. SFV, however, believed to enter cells from the early endosome, was unaffected by PKCβII T500V expression. We also examined the trafficking of two cellular ligands, transferrin and epidermal growth factor (EGF). PKCβII T500V expression specifically blocked EGF receptor trafficking and degradation, without affecting transferrin receptor recycling. As with influenza virus, in PKCβII kinase-dead cells, EGF receptor was trapped in a late endosome compartment. Our findings suggest that PKCβII is an important regulator of a late endosomal sorting event needed for influenza virus entry and infection.