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Journal of General Virology (2000), 81, 327-334.
© 2000 Society for General Microbiology


Animal: DNA Viruses

{alpha}6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4

Gary Sibbet1, Christine Romero-Graillet2, Guerrino Meneguzzi2 and M. Saveria Campob,1

Beatson Institute for Cancer Research, Garscube Estate, Glasgow G61 1QH, UK1
INSERM U385, Faculty of Medicine, University of Nice, Nice, France2

Author for correspondence: Gary Sibbet. Fax +44 141 942 6521. e-mail g.sibbet{at}beatson.gla.ac.uk

Recently, {alpha}6 integrin has been proposed as the epithelial cell receptor for papillomavirus. This study investigated whether {alpha}6 integrin is the cellular receptor for bovine papillomavirus type 4 (BPV-4), which is strictly epitheliotropic and infects the mucous epithelium of the upper digestive tract. Primary bovine mucosal keratinocytes from the palate of a foetus (PalK) displayed high levels of {alpha}6 integrin; matched primary fibroblasts from the same biopsy (PalF) expressed almost no {alpha}6 integrin. However, BPV-4 bound both PalK and PalF to similar, saturable levels. Native BPV-4 virions infected PalK in vitro, as detected by RT–PCR of E7 RNA. Infection could be blocked by excess virus-like particles (VLPs) and by neutralizing antisera against L1–L2 and L1 VLPs or by denaturation of the virions, supporting the view that infection in vitro mimics the process in vivo. {alpha}6 integrin-negative human keratinocyte cell lines were derived from patients affected by junctional epidermolysis bullosa presenting genetic lesions in their hemidesmosomes. The level of {alpha}6 integrin expression was determined in these cell lines by in situ immunofluorescence and FACS. Despite the absence of {alpha}6 integrin expression by BO-SV cells, they were bound by BPV-4 to similar, saturable levels as normal keratinocytes, KH-SV. Furthermore, BO-SV and KH-SV cells were both infected by BPV-4 to apparently the same extent as PalK cells. These results are consistent with the conclusion that {alpha}6 integrin is not the obligatory receptor for a bovine mucosotropic papillomavirus.




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