Cottontail rabbit papillomavirus E8 protein is essential for wart formation and provides new insights into viral pathogenesis
| Autor: | Jerome Salmon, Mathieu Nonnenmacher, Gérard Orth, Yves Jacob, Françoise Breitburd |
|---|---|
| Přispěvatelé: | Papillomavirus, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement of Pharmacology and Molecular Sciences, Johns Hopkins University (JHU), Génétique, Papillomavirus et Cancer Humain, Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP) |
| Rok vydání: | 2006 |
| Předmět: |
MESH: Neoplasm Proteins
MESH: Epidermal Growth Factor Viral pathogenesis MESH: Rabbits MESH: Amino Acid Sequence Cottontail rabbit papillomavirus MESH: Cadherins Transformation and Oncogenesis 0302 clinical medicine Epidermal growth factor MESH: Cottontail rabbit papillomavirus MESH: Animals Cation Transport Proteins Oncogene Proteins 0303 health sciences virus diseases Cadherins Transmembrane protein MESH: Transcription Factor AP-1 3. Good health Cell biology Transport protein Neoplasm Proteins 030220 oncology & carcinogenesis [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Membrane Proteins Rabbits Warts Endosome MAP Kinase Signaling System Immunology Molecular Sequence Data Biology MESH: Two-Hybrid System Techniques Microbiology Cell Line 03 medical and health sciences MESH: Cation Transport Proteins Viral Proteins MESH: Oncogene Proteins Virology Two-Hybrid System Techniques Animals Humans Amino Acid Sequence 030304 developmental biology MESH: Molecular Sequence Data MESH: Humans Epidermal Growth Factor MESH: MAP Kinase Signaling System MESH: Warts Membrane Proteins MESH: Viral Proteins Protocadherins MESH: Cell Line Transcription Factor AP-1 Open reading frame Membrane protein Insect Science |
| Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2006, 80 (10), pp.4890-900. ⟨10.1128/JVI.80.10.4890-4900.2006⟩ Journal of Virology, 2006, 80 (10), pp.4890-900. ⟨10.1128/JVI.80.10.4890-4900.2006⟩ |
| ISSN: | 0022-538X 1098-5514 |
| DOI: | 10.1128/JVI.80.10.4890-4900.2006⟩ |
| Popis: | The cottontail rabbit papillomavirus (CRPV) a and b subtypes display a conserved E8 open reading frame encoding a 50-amino-acid hydrophobic protein, with structural similarities to the E5 transmembrane oncoprotein of genital human PVs (HPVs). CRPV E8 has been reported to play a role in papilloma growth but not to be essential in papilloma formation. Here we report that the knockout of E8 start codon almost prevented wart induction upon biobalistic inoculation of viral DNA onto rabbit skin. The scarce warts induced showed very slow growth, despite sustained expression of E6 and E7 oncogenes. This points to an essential role of E8 in disturbing epidermal homeostasis. Using a yeast two-hybrid screen, we found that E8 interacted with the zinc transporter ZnT1, protocadherin 1 (PCDH1), and AHNAK/desmoyokin, three proteins as yet unrelated to viral pathogenesis or cell transformation. HPV16 E5 also interacted with these proteins in two-hybrid assay. CRPV E8 mainly localized to the Golgi apparatus and the early endosomes of transfected keratinocytes and colocalized with ZnT1, PCDH1, and AHNAK. We showed that ZnT1 and PCDH1 formed a complex and that E8 disrupted this complex. CRPV E8, like HPV16 E5, increased epidermal growth factor (EGF)-dependent extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and both the EGF-dependent and the EGF-independent activity of activating protein-1 (AP-1). Competition experiments with a nonfunctional truncated ZnT1 protein showed that E8-ZnT1 interaction was required for AP-1 activation. Our data identify CRPV E8 as a key player in papilloma induction and unravel novel cellular targets for inducing the proliferation of keratinocytes. |
| Databáze: | OpenAIRE |
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