Suprabasal overexpression of Beta-1 integrin is induced by bovine papillomavirus type 1

• Published in: Virology (New York, N.Y.) N.Y.), 2006-11, Vol.355 (1), p.102-114
• Main Authors: Cooper, Brooke, Brimer, Nicole, Stoler, Mark, Vande Pol, Scott B.
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Bovine papillomavirus; Bovine papillomavirus 1 - physiology; Cattle; cattle diseases; Cell Line; cultured cells; DNA - biosynthesis; epidermal growth factor; Epithelium - pathology; Epithelium - virology; Gene Expression Regulation; gene overexpression; glycoproteins; Histocytochemistry; Humans; In Situ Hybridization; Integrin; Integrin beta1 - biosynthesis; integrins; Keratinocytes - virology; MAP Kinase Kinase Kinase 3 - biosynthesis; Microscopy, Fluorescence; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - physiology; Oncoprotein; Papilloma - immunology; Papilloma - pathology; Papilloma - virology; Papillomavirus Infections - immunology; Papillomavirus Infections - virology; Psoriasis; RNA - biosynthesis; RNA - genetics; transcription (genetics); viral envelope proteins; viral proteins; Virus Replication
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.06.032

In a normal stratified squamous epithelium, β1-integrin is expressed in basal epithelial cells. In BPV-induced fibropapillomas β1-integrin is overexpressed and aberrantly localized, with uniform expression in the lower spinous layer, and sporadic expression within the mid-spinous region that co-localizes with expression of the viral E5 and E7 oncoproteins. In situ hybridization of fibropapillomas for β1-integrin RNA revealed sporadic hybridization in the spinous layer, indicating transcriptional induction. β1-integrin expression in cultured keratinocytes requires exogenous EGF in the media, but this requirement is lost if E7 is expressed, and E7 was able to abrogate the EGF-requirement of normal keratinocytes for the activation of ERK and DNA synthesis. Within fibropapillomas, suprabasal expression of E5 and E7 correlated with suprabasal expression of β1-integrin and PCNA, indicating that vegetative viral replication in the spinous layer correlated with the expression of E7 and β1 integrin. The ability of BPV-1 E7 to support β1-integrin expression and EGF independent DNA synthesis and the activation of ERK are the first biochemical correlates of its expression in keratinocytes.