Cytopathic Effect in Human Papillomavirus Type 1–Induced Inclusion Warts: In Vitro Analysis of the Contribution of Two Forms of the Viral E4 Protein
| Autor: | Claire Rogel-Gaillard, Gérard Orth, Françoise Breitburd, Gérard Pehau-Arnaudet |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Keratinocytes
Immunoelectron microscopy Molecular Sequence Data Fluorescent Antibody Technique Dermatology Biology Cytoplasmic Granules Biochemistry Cell Line Gene product Cytokeratin Cytopathogenic Effect Viral immunoelectron microscopy Tumor Cells Cultured Animals Humans myrmecia wart Amino Acid Sequence Intermediate filament Microscopy Immunoelectron Papillomaviridae Molecular Biology Cytopathic effect Inclusion Bodies Cell Biology Fusion protein Virology Molecular biology Cytoplasm Ultrastructure Keratins Rabbits intermediate filament-associated protein cytokeratin Adenovirus E4 Proteins |
| Zdroj: | Journal of Investigative Dermatology. 101(6):843-851 |
| ISSN: | 0022-202X |
| DOI: | 10.1111/1523-1747.ep12371705 |
| Popis: | Myrmecia warts induced by human papillomavirus type 1 (HPV1) are characterized by abundant eosinophilic inclusions associated with HPV1 E4 gene products. The major HPV1 E4 proteins are a 17-kilodalton (kDa) E1-E4 fusion protein and a 16-kDa species lacking the five E1 aminoacids and a few E4 residues. To study the contribution of E4 proteins to the formation of myrmecia inclusions, we used a previously designed transient expression system in the rabbit VX2-R keratinocyte line. We find that the E1-E4 and an E4 protein without the E1 residues (E4-3200) form eosinophilic inclusions. Ultrastructural and immunoelectron microscopic studies show that the electron-dense, keratohyalin-like myrmecia inclusions are recognized by anti-E4 antibodies. They are associated with tonofilament bundles at their periphery in the cytoplasm or free of filaments in the nucleus. The E1–E4 inclusions formed in vitro are also homogeneously electron dense, and are usually associated with tonofilaments at their periphery in the cytoplasm and free of filaments in the nucleus. The E4-3200 inclusions are exclusively cytoplasmic and heterogeneously electron dense, with a fibrillar structure made of entangled 10-nm filaments. The expression of either protein in VX2-R cells does not result in the collapse of the cytokeratin network, as shown by immunofluorescence double-labeling experiments. This is in contrast to data reported for the HPV16 E1–E4 protein. Our findings indicate that the E1–E4 protein by itself accounts for the formation of myrmecia inclusions, and suggest that the five N-terminal E1 aminoacids play a major role in the interaction of E4 proteins with intermediate filaments. |
| Databáze: | OpenAIRE |
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