ADAM17-dependent signaling is required for oncogenic Human Papilloma virus entry platform assembly
- University Medical Center of the Johannes Gutenberg University Mainz, Germany
- University of Bonn, Germany
- University Hospital Schleswig-Holstein Campus, Germany
Abstract
Oncogenic Human papillomaviruses (HPV) are small DNA viruses that infect keratinocytes. After HPV binding to cell surface receptors a cascade of molecular interactions mediates the infectious cellular internalization of virus particles. Aside from the virus itself, important molecular players involved in virus entry include the tetraspanin CD151 and the epidermal growth factor receptor (EGFR). To date, it is unknown how these components are coordinated in space and time. Here, we studied plasma membrane dynamics of CD151 and EGFR and the HPV16 capsid during the early phase of infection. We find that the proteinase ADAM17 activates the extracellular signal regulated kinases (ERK1/2) pathway by the shedding of growth factors that trigger the formation of an endocytic entry platform. Infectious endocytic entry platforms carrying virus particles consist of two-fold larger CD151 domains containing the EGFR. Our finding clearly dissects initial virus binding from ADAM17-dependent assembly of a HPV/CD151/EGFR entry platform.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Deutsche Forschungsgemeinschaft (FL 696/3-1)
- Thorsten Lang
- Luise Florin
Deutscher Akademischer Austauschdienst
- Snježana Mikuličić
Deutsche Forschungsgemeinschaft (LA 1272/8-1)
- Thorsten Lang
- Luise Florin
Deutsche Forschungsgemeinschaft (CRC877 (A4))
- Karina Reiss
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Mikuličić et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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ADAM17-dependent signaling is required for oncogenic Human Papilloma virus entry platform assembly
eLife 8:e44345.
https://doi.org/10.7554/eLife.44345
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