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

Cell Struct Funct. 2019 Apr 25;44(1):61-74. doi: 10.1247/csf.19001. Epub 2019 Mar 21.


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.Key words: signal transduction, endocytosis, endosome, imaging, influenza virus.

Keywords: endocytosis; endosome; imaging; influenza virus; signal transduction.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Endocytosis / drug effects*
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Humans
  • Orthomyxoviridae / drug effects*
  • Orthomyxoviridae / physiology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Phosphatidylinositol 3-Kinase / chemistry*
  • Protein Transport / drug effects
  • Virus Internalization / drug effects
  • ras Proteins / metabolism


  • Peptide Fragments
  • Phosphatidylinositol 3-Kinase
  • ras Proteins