Autoren:	Mikuličić, Snježana Fritzen, Anna Scheffer, Konstanze Strunk, Johannes Cabañas, Carlos Sperrhacke, Maria Reiss, Karina Florin, Luise
Titel:	Tetraspanin CD9 affects HPV16 infection by modulating ADAM17 activity and the ERK signalling pathway
Online-Publikationsdatum:	11-Mai-2021
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Human papillomaviruses (HPV) are causative agents of various tumours such as cervical cancer. HPV binding to the cell surface of keratinocytes leads to virus endocytosis at tetraspanin enriched microdomains. Complex interactions of the capsid proteins with host proteins as well as ADAM17-dependent ERK1/2 signal transduction enable the entry platform assembly of the oncogenic HPV type 16. Here, we studied the importance of tetraspanin CD9, also known as TSPAN29, in HPV16 infection of different epithelial cells. We found that both overexpression and loss of the tetraspanin decreased infection rates in cells with low endogenous CD9 levels, while reduction of CD9 expression in keratinocytes that exhibit high-CD9 protein amounts, led to an increase of infection. Therefore, we concluded that low-CD9 supports infection. Moreover, we found that changes in CD9 amounts affect the shedding of the ADAM17 substrate transforming growth factor alpha (TGFα) and the downstream phosphorylation of ERK. These effects correlate with those on infection rates suggesting that a specific CD9 optimum promotes ADAM17 activity, ERK signalling and virus infection. Together, our findings implicate that CD9 regulates HPV16 infection through the modulation of ADAM17 sheddase activity.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5772
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Medical microbiology and immunology 209
Seitenzahl oder Artikelnummer:	461 471
Verlag:	Springer
Verlagsort:	Berlin u.a.
Erscheinungsdatum:	2020
ISSN:	1432-1831
URL der Originalveröffentlichung:	https://doi.org/10.1007/s00430-020-00671-5
DOI der Originalveröffentlichung:	10.1007/s00430-020-00671-5
Enthalten in den Sammlungen:	JGU-Publikationen