A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection

Cell Structure and Function

Kosui Horiuchi¹  Aya O. Satoh²  Yoichiro Fujioka³ 

[1] Department of Biochemical Pathophysiology, Medical Research Institute, Tokyo Medical and Dental University;Department of Biological Sciences and Engineering, Faculty of Health Sciences, Hokkaido University;Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University

关键词: signal transduction;    endocytosis;    endosome;    imaging;    influenza virus;   

DOI  :  10.1247/csf.19001

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

Endocytosis mediates the internalization and ingestion of a variety of endogenous or exogenous substances, including virus particles, under the control of intracellular signaling pathways. We have previously reported that the complex formed between the small GTPase Ras and phosphoinositide 3-kinase (PI3K) translocates from the plasma membrane to endosomes, signaling from which thereby regulates clathrin-independent endocytosis, endosome maturation, influenza virus internalization, and infection. However, the molecular mechanism by which the Ras-PI3K complex is recruited to endosomes remains unclear. Here, we have identified the amino acid sequence responsible for endosomal localization of the Ras-PI3K complex. PI3K lacking this sequence failed to translocate to endosomes, and expression of the peptide comprising this PI3K-derived sequence inhibited clathrin-independent endocytosis, influenza virus internalization, and infection. Moreover, treatment of cells with this peptide in an arginine-rich, cell-penetrating form successfully suppressed influenza virus infection in vitro and ex vivo, making this peptide a potential therapeutic agent against influenza virus infection.

【 授权许可】

Unknown