alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4

Recently, alpha6 integrin has been proposed as the epithelial cell receptor for papillomavirus. This study investigated whether alpha6 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 alpha6 integrin; matched primary fibroblasts from the same biopsy (PalF) expressed almost no alpha6 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. alpha6 integrin-negative human keratinocyte cell lines were derived from patients affected by junctional epidermolysis bullosa presenting genetic lesions in their hemidesmosomes. The level of alpha6 integrin expression was determined in these cell lines by in situ immunofluorescence and FACS. Despite the absence of alpha6 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 alpha6 integrin is not the obligatory receptor for a bovine mucosotropic papillomavirus.