ADAM17-dependent signaling is required for oncogenic Human Papilloma virus entry platform assembly

  1. Snježana Mikuličić
  2. Jérôme Finke
  3. Fatima Boukhallouk
  4. Elena Wüstenhagen
  5. Dominik Sons
  6. Yahya Homsi
  7. Karina Reiss
  8. Thorsten Lang
  9. Luise Florin  Is a corresponding author
  1. University Medical Center of the Johannes Gutenberg University Mainz, Germany
  2. University of Bonn, Germany
  3. 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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Snježana Mikuličić

    Institute for Virology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Jérôme Finke

    Department of Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Fatima Boukhallouk

    Department of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Elena Wüstenhagen

    Institute for Virology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5420-6536
  5. Dominik Sons

    Department of Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Yahya Homsi

    Department of Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Karina Reiss

    Department of Dermatology and Allergology, University Hospital Schleswig-Holstein Campus, Kiel, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Thorsten Lang

    Department of Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9128-0137
  9. Luise Florin

    Institute for Virology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    For correspondence
    lflorin@uni-mainz.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4310-7329

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.

Reviewing Editor

  1. Pamela J Bjorkman, California Institute of Technology, United States

Publication history

  1. Received: December 12, 2018
  2. Accepted: May 17, 2019
  3. Accepted Manuscript published: May 20, 2019 (version 1)
  4. Version of Record published: June 10, 2019 (version 2)

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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  1. Snježana Mikuličić
  2. Jérôme Finke
  3. Fatima Boukhallouk
  4. Elena Wüstenhagen
  5. Dominik Sons
  6. Yahya Homsi
  7. Karina Reiss
  8. Thorsten Lang
  9. Luise Florin
(2019)
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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