A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection

被引：80

作者：

Fujioka, Yoichiro ^{[1
]}

Tsuda, Masumi ^{[2
]}

Nanbo, Asuka ^{[1
]}

Hattori, Tomoe ^{[3
]}

Sasaki, Junko ^{[4
]}

Sasaki, Takehiko ^{[4
]}

Miyazaki, Tadaaki ^{[3
]}

Ohba, Yusuke ^{[1
]}

机构：

[1] Hokkaido Univ, Grad Sch Med, Dept Cell Physiol, Sapporo, Hokkaido 0608638, Japan

[2] Hokkaido Univ, Grad Sch Med, Dept Canc Pathol, Sapporo, Hokkaido 0608638, Japan

[3] Hokkaido Univ, Res Ctr Zoonosis Control, Dept Bioresources, Sapporo, Hokkaido 0600020, Japan

[4] Akita Univ, Grad Sch Med, Dept Med Biol, Akita 0108543, Japan

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

PHOSPHATIDYLINOSITOL; 4-PHOSPHATE; 5-KINASE; CLATHRIN-INDEPENDENT ENDOCYTOSIS; LIVING CELLS; R-RAS; PHOSPHOLIPASE-C; MATRIX PROTEIN; SMOOTH-MUSCLE; CANCER CELLS; VIRAL ENTRY; RHO-GTPASES;

D O I：

10.1038/ncomms3763

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Various viruses enter host cells via endocytosis, but the molecular mechanisms underlying the specific internalization pathways remain unclear. Here we show that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin-mediated and clathrin-independent endocytosis, with intracellular Ca2+ having a central role in regulation of both pathways by activating a signalling axis comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic Ca2+ concentration of host cells, the prevention of which markedly attenuates virus internalization and infection. The small GTPase RhoA is found both to function downstream of the virus-induced Ca2+ response and itself to induce Ca2+ oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC signalling. This signalling circuit regulates both clathrin-mediated and clathrin-independent endocytosis during virus infection and seems to constitute a key mechanism for regulation of IAV internalization and infection.

引用

页数：13

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