The Ras-PI3K Signaling Pathway Is Involved in Clathrin-Independent Endocytosis and the Internalization of Influenza Viruses

Fujioka Yoichiro; Tsuda Masumi; Hattori Tomoe; Sasaki Junko; Sasaki Takehiko; Miyazaki Tadaaki; Ohba Yusuke

Title	en The Ras-PI3K Signaling Pathway Is Involved in Clathrin-Independent Endocytosis and the Internalization of Influenza Viruses
Creator	en Fujioka, Yoichiro en Tsuda, Masumi en Hattori, Tomoe en Sasaki, Junko en Sasaki, Takehiko en Miyazaki, Tadaaki NRID 1000060272431 en Ohba, Yusuke
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/2.5/ en Creative Commons Attribution
Subject	NDC 493
Description	Abstract en Background: 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. Methodology/Principal Findings: 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 clathrinin-dependent 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. Conclusions/Significance: 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.
Publisher	en Public Library of Science
Date	Issued2011-01-20
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/44993
Relation	isIdenticalTo DOI https://doi.org/10.1371/journal.pone.0016324
Journal	PISSN 1932-6203 en PLoS One Volume Number6 Issue Number1 Page Starte16324
File	fulltext PLoSONE6-1_e16324.pdf 1.03 MB (application/pdf) Issued2011-01-20
Oaidate	2023-07-26