α6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4

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.