title: The epidermal growth factor receptor (EGFR) promotes uptake of influenza A viruses (IAV) into host cells.
abstract: Influenza A viruses (IAV) bind to sialic-acids at cellular surfaces and enter cells by using endocytotic routes. There is evidence that this process does not occur constitutively but requires induction of specific cellular signals, including activation of PI3K that promotes virus internalization. This implies engagement of cellular signaling receptors during viral entry. Here, we present first indications for an interplay of IAV with receptor tyrosine kinases (RTKs). As representative RTK family-members the epidermal growth factor receptor (EGFR) and the c-Met receptor were studied. Modulation of expression or activity of both RTKs resulted in altered uptake of IAV, showing that these receptors transmit entry relevant signals upon virus binding. More detailed studies on EGFR function revealed that virus binding lead to clustering of lipid-rafts, suggesting that multivalent binding of IAV to cells induces a signaling platform leading to activation of EGFR and other RTKs that in turn facilitates IAV uptake.
authors.affiliation: Institute of Molecular Virology, ZMBE, Westfälische-Wilhelms-University, Münster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Eierhoff
authors.forename: Eike R
authors.initials: ER
authors.lastname: Hrincius
authors.forename: Ursula
authors.initials: U
authors.lastname: Rescher
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
mesh_terms: D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002462:Cell Membrane / Q000821:virology*; D002478:Cells, Cultured; D004285:Dogs; D004705:Endocytosis; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015398:Signal Transduction
chemical_list: D066246:ErbB Receptors