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Authors: Mikuličić, Snježana
Fritzen, Anna
Scheffer, Konstanze
Strunk, Johannes
Cabañas, Carlos
Sperrhacke, Maria
Reiss, Karina
Florin, Luise
Title: Tetraspanin CD9 affects HPV16 infection by modulating ADAM17 activity and the ERK signalling pathway
Online publication date: 11-May-2021
Year of first publication: 2020
Language: english
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: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Medical microbiology and immunology
Pages or article number: 461
Publisher: Springer
Publisher place: Berlin u.a.
Issue date: 2020
ISSN: 1432-1831
Publisher URL:
Publisher DOI: 10.1007/s00430-020-00671-5
Appears in collections:JGU-Publikationen

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