ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly

• Published in: eLife 2019-05, Vol.8
• Main Authors: Mikuličić, Snježana, Finke, Jérôme, Boukhallouk, Fatima, Wüstenhagen, Elena, Sons, Dominik, Homsi, Yahya, Reiss, Karina, Lang, Thorsten, Florin, Luise
• Format: Article
• Language: English
• Subjects: ADAM17; ADAM17 Protein - genetics; Carcinogenesis - genetics; Cell Biology; Cell Membrane - virology; Cell membranes; Cell surface; Cellular signal transduction; DNA; DNA viruses; Endocytosis - genetics; entry receptor complex; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; ErbB Receptors - genetics; Extracellular signal-regulated kinase; Growth factors; Health aspects; HeLa Cells; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - pathogenicity; Humans; Infection; Infections; Internalization; Keratinocytes; Keratinocytes - metabolism; Keratinocytes - virology; MAP Kinase Signaling System - genetics; Microbiology and Infectious Disease; microdomains; Microscopy; oncogenic Papillomavirus; Papillomaviridae; Papillomaviridae - genetics; Papillomaviridae - pathogenicity; Papillomavirus; Papillomavirus infections; Papillomavirus Infections - genetics; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Physiological aspects; Proteinase; Signal transduction; Surface science; tetraspanin; Tetraspanin 24 - genetics; Tumors; Viral infections; Viral proteins; Virion - genetics; Virion - pathogenicity; Virus Internalization; Viruses
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.44345

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 which triggers 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.