6533b837fe1ef96bd12a1e32
RESEARCH PRODUCT
false
Snježana MikuličićJérôme FinkeFatima BoukhalloukElena WüstenhagenDominik SonsYahya HomsiKarina ReissThorsten LangLuise Florinsubject
Keratinocytes0301 basic medicineCarcinogenesisvirusesEndocytic cycle610 MedizinTetraspanin610 Medical sciencesEpidermal growth factor receptorBiology (General)InternalizationPapillomaviridaemedia_commonHuman papillomavirus 16Microbiology and Infectious DiseaseADAM17General NeuroscienceQRoncogenic PapillomavirusGeneral MedicineEndocytosisCell biologyErbB ReceptorsCapsidMedicinemicrodomainsResearch ArticleHumanQH301-705.5MAP Kinase Signaling SystemSciencemedia_common.quotation_subject030106 microbiologyADAM17 ProteinTetraspanin 24BiologyGeneral Biochemistry Genetics and Molecular BiologyVirus03 medical and health sciencesCell surface receptorViral entrygrowth factorsHumansGeneral Immunology and MicrobiologyCell MembranePapillomavirus InfectionsVirionentry receptor complexCell BiologyVirus Internalizationtetraspanin030104 developmental biologybiology.proteinHeLa Cellsdescription
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.
year | journal | country | edition | language |
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2018-12-12 | eLife |