The Ras-PI3K signaling pathway is involved in clathrin-independent endocytosis and the internalization of influenza viruses.
The Ras-PI3K signaling pathway is involved in clathrin-independent endocytosis and the internalization of influenza viruses.
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DOI：
10.1371/journal.pone.0016324
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Ohba Y
中科院分区：
文献类型：
--
作者：
Fujioka Y;Tsuda M;Hattori T;Sasaki J;Sasaki T;Miyazaki T;Ohba Y
流感病毒感染引起高度传染性的严重呼吸系统疾病，每年导致数千人死亡;然而，目前批准的防御策略，包括疫苗和神经氨酸酶抑制剂的功效有限，因为病毒经常通过抗原漂移和重配获得抗性。因此，重要的是要建立一种新的，有效的治疗策略，是有效的病毒亚型无关。在这里，我们确定Ras-磷酸肌醇3-激酶（PI 3 K）信号通路作为流感病毒进入宿主细胞的调节机制。Ras与PI 3 K的结合特异性地涉及病毒的网格蛋白非依赖性内吞作用、内体成熟和细胞内转运，这导致不同亚型的流感病毒在缺乏Ras-PI 3 K相互作用的细胞中的感染效力降低。此外，流感病毒感染确实在早期内体中触发Ras活化和随后的PI 3 K活化。综上所述，这些结果表明Ras-PI 3 K信号传导轴作为病毒内化的宿主导向机制。鉴于病毒掺入是病毒亚型和物种中保守的过程，该信号传导途径可以为针对广泛病毒的有效、耐受性良好的药物和治疗剂提供靶标。
Influenza virus infection causes highly contagious, severe respiratory disorders and gives rise to thousands of deaths every year; however, the efficacy of currently approved defense strategies, including vaccines and neuraminidase inhibitors, is limited because the virus frequently acquires resistance via antigen drift and reassortment. It is therefore important to establish a novel, effective therapeutic strategy that is effective irrespective of viral subtype. Here, we identify the Ras–phosphoinositide 3-kinase (PI3K) signaling pathway as a host-cell regulatory mechanism for influenza virus entry. The binding of Ras to PI3K is specifically involved in clathrin-independent endocytosis, endosomal maturation, and intracellular transport of viruses, which result in decreased infectious efficacy of different subtypes of influenza viruses in cells lacking the Ras–PI3K interaction. Moreover, influenza virus infection indeed triggered Ras activation and subsequent PI3K activation in early endosomes. Taken together, these results demonstrate that the Ras–PI3K signaling axis acts as a host-oriented mechanism for viral internalization. Given that virus incorporation is a process conserved among virus subtypes and species, this signaling pathway may provide a target for potent, well-tolerated prophylactics and therapeutics against a broad range of viruses.
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影响因子：
11.2
作者：
Inuzuka, Takayuki;Tsuda, Masumi;Ohba, Yusuke
通讯作者：
Ohba, Yusuke
影响因子：
3.4
作者：
Acosta, Eliana G.;Castilla, Viviana;Damonte, Elsa B.
通讯作者：
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DOI：
10.1073/pnas.0803711105
发表时间：
2008-08-19
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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