The epidermal growth factor receptor (EGFR) promotes uptake of influenza A viruses (IAV) into host cells

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. Th...

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Bibliographic Details
Published in:PLoS pathogens 2010-09, Vol.6 (9), p.e1001099-e1001099
Main Authors: Eierhoff, Thorsten, Hrincius, Eike R, Rescher, Ursula, Ludwig, Stephan, Ehrhardt, Christina
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Blotting, Western
Cell Membrane - virology
Cells, Cultured
Colleges & universities
Dogs
Endocytosis
Epidermal growth factor
ErbB Receptors - genetics
ErbB Receptors - metabolism
Fluorescent Antibody Technique
Humans
Immunoenzyme Techniques
Immunoprecipitation
Influenza A virus - physiology
Influenza virus
Influenza, Human - metabolism
Influenza, Human - pathology
Influenza, Human - virology
Kinases
Mice
Orthomyxoviridae Infections - metabolism
Orthomyxoviridae Infections - pathology
Orthomyxoviridae Infections - virology
Phosphorylation
Plasma
Proteins
Signal Transduction
Virology/Host Invasion and Cell Entry
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1001099