Integrin β1 Mediates Vaccinia Virus Entry through Activation of PI3K/Akt Signaling

被引:88
作者
Izmailyan, Roza [1 ]
Hsao, Jye-Chian [1 ]
Chung, Che-Sheng [1 ]
Chen, Chein-Hung [2 ]
Hsu, Paul Wei-Che [1 ]
Liao, Chung-Lin [2 ]
Chang, Wen [1 ]
机构
[1] Acad Sinica, Inst Mol Biol, Taipei, Taiwan
[2] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan
关键词
INTRACELLULAR MATURE VIRUS; FOCAL ADHESION KINASE; MEMBRANE-PROTEIN; CELL-ADHESION; IDENTIFICATION; VIRIONS; SURFACE; FUSION; PENETRATION; EXPRESSION;
D O I
10.1128/JVI.06860-11
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Vaccinia virus has a broad range of infectivity in many cell lines and animals. Although it is known that the vaccinia mature virus binds to cell surface glycosaminoglycans and extracellular matrix proteins, whether additional cellular receptors are required for virus entry remains unclear. Our previous studies showed that the vaccinia mature virus enters through lipid rafts, suggesting the involvement of raft-associated cellular proteins. Here we demonstrate that one lipid raft-associated protein, integrin beta 1, is important for vaccinia mature virus entry into HeLa cells. Vaccinia virus associates with integrin beta 1 in lipid rafts on the cell surface, and the knockdown of integrin beta 1 in HeLa cells reduces vaccinia mature virus entry. Additionally, vaccinia mature virus infection is reduced in a mouse cell line, GD25, that is deficient in integrin beta 1 expression. Vaccinia mature virus infection triggers the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling, and the treatment of cells with inhibitors to block PI3K activation reduces virus entry in an integrin beta 1-dependent manner, suggesting that integrin beta 1-mediates PI3K/Akt activation induced by vaccinia virus and that this signaling pathway is essential for virus endocytosis. The inhibition of integrin beta 1-mediated cell adhesion results in a reduction of vaccinia virus entry and the disruption of focal adhesion and PI3K/Akt activation. In summary, our results show that the binding of vaccinia mature virus to cells mimics the outside-in activation process of integrin functions to facilitate vaccinia virus entry into HeLa cells.
引用
收藏
页码:6677 / 6687
页数:11
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