Recently, alpha 6 integrin has been proposed as the epithelial cell recepto
r for papillomavirus. This study investigated whether alpha 6 integrin is t
he cellular receptor for bovine papillomavirus type 4 (BPV-4), which is str
ictly epitheliotropic and infects the mucous epithelium of the upper digest
ive tract. Primary bovine mucosal keratinocytes from the palate of a foetus
(PalK) displayed high levels of alpha 6 integrin; matched primary fibrobla
sts from the same biopsy (PalF) expressed almost no alpha 6 integrin. Howev
er, 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. Infecti
on could be blocked by excess virus-like particles (VLPs) and by neutralizi
ng antisera against L1-L2 and L1 VLPs or by denaturation of the virions, su
pporting the view that infection in vitro mimics the process in vivo. alpha
6 integrin-negative human keratinocyte cell lines were derived from patien
ts affected by junctional epidermolysis bullosa presenting genetic lesions
in their hemidesmosomes. The level of alpha 6 integrin expression was deter
mined in these cell lines by in situ immunofluorescence and FACS. Despite t
he absence of alpha 6 integrin expression by BO-SV cells, they were bound b
y BPV-4 to similar, saturable levels as normal keratinocytes, KH-SV, Furthe
rmore, 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 mucosotr
opic papillomavirus.