Echovirus 1 internalization negatively regulates epidermal growth factor receptor downregulation
Huttunen, M., Turkki, P., Mäki, A., Paavolainen, L., Ruusuvuori, P., & Marjomäki, V. (2017). Echovirus 1 internalization negatively regulates epidermal growth factor receptor downregulation. Cellular Microbiology, 19(3), Article e12671. https://doi.org/10.1111/cmi.12671
Published inCellular Microbiology
© 2016 John Wiley & Sons. This is a final draft version of an article whose final and definitive form has been published by Wiley. Published in this repository with the kind permission of the publisher.
We have demonstrated previously that the human picornavirus Echovirus 1 (EV1) triggers an infectious internalization pathway that follows closely, but seems to stay separate, from the epidermal growth factor receptor (EGFR) pathway triggered by epidermal growth factor (EGF). Here, we confirmed by using live and confocal microscopy that EGFR and EV1 vesicles are following intimately each other but are distinct entities with different degradation kinetics. We show here that despite being sorted to different pathways and located in distinct endosomes, EV1 inhibits EGFR downregulation. Simultaneous treatment with EV1 and EGF led to an accumulation of EGFR in cytoplasmic endosomes, which was evident already 15 min p.i. and more pronounced after 2 hr p.i. EV1 treatment led to reduced downregulation, which was proven by increased total cellular amount of EGFR. Confocal microscopy studies revealed that EGFR accumulated in large endosomes, presumably macropinosomes, which were not positive for markers of the early, recycling, or late endosomes/lysosomes. Interestingly, EV1 did not have a similar blocking effect on bulk endosomal trafficking or transferrin recycling along the clathrin pathway suggesting that EV1 did not have a general effect on cellular trafficking pathways. Importantly, EGF treatment increased EV1 infection and increased cell viability during infection. Simultaneous EV1 and EGF treatment seemed to moderately enhance phosphorylation of protein kinase C α. Furthermore, similar phenotype of EGFR trafficking could be produced by phorbol 12‐myristate 13‐acetate treatment, further suggesting that activated protein kinase C α could be contributing to EGFR phenotype. These results altogether demonstrate that EV1 specifically affects EGFR trafficking, leading to EGFR downregulation, which is beneficial to EV1 infection. ...
PublisherWiley-Blackwell Publishing Ltd
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Additional information about fundingAcademy of Finland. Grant Number: 257125
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