A1 Journal article (refereed)
Echovirus 1 internalization negatively regulates epidermal growth factor receptor downregulation (2017)


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


JYU authors or editors


Publication details

All authors or editors: Huttunen, Moona; Turkki, Paula; Mäki, Anita; Paavolainen, L.; Ruusuvuori, P.; Marjomäki, Varpu

Journal or series: Cellular Microbiology

ISSN: 1462-5814

eISSN: 1462-5822

Publication year: 2017

Volume: 19

Issue number: 3

Article number: e12671

Publisher: Wiley-Blackwell Publishing Ltd

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1111/cmi.12671

Publication open access: Not open

Publication channel open access:

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/53034


Abstract

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.


Keywords: degradation; endocytosis

Free keywords: enterovirus; epidermal growth factor receptor (EGFR); signaling


Contributing organizations


Ministry reporting: Yes

Reporting Year: 2017

JUFO rating: 2


Last updated on 2021-08-06 at 15:08