This may be dependent on the viruses used and their passage histories. The sequence of phocine PVRL4 has not been published and is not found in Genbank. However, canine PVRL4 shares 94% identity with the human sequence. Therefore, members of the carnivore, i.e. seal and dog sequences would be predicted to have even higher similarity. Furthermore, morbilliviruses have been shown to bind to the V domain of PVRL4 with the virus H protein Gefitinib binding site being highly conserved. This would explain why wtPDV can readily use human PVRL4 and suggests that the virus could also use this molecule in vivo. Unlike wt MV and wtCDV, wt strains of PDV were found to infect Vero cells with no prior adaptation. In common with RPV and CDV we have demonstrated that wtPDV does not utilise CD46 as a receptor. These results further support the presence of another receptor for wtPDV which we have identified as proHB-EGF on Vero cells. This molecule is also expressed on EBV transformed B cells and may therefore explain why infection of wtPDV was only slightly reduced by anti-SLAM antibody treatment of B95a cells. However, wtCDV infection of B95A cells was also only slightly reduced and may indicate a further unknown receptor on these cells for morbilliviruses. The number of proHB-EGF molecules on the surface of Vero cells is at least 100-fold less than CD9 molecules. The low density of the receptor may result in relatively reduced virus entry and slower virus spread which would explain why 5 days are required to get good infection levels of wtPDV and limited fusion occurs in Vero compared to VDS cells. wtCDV showed little or no infection of Vero cells and anti HB-EGF antibody did not inhibit infection by the Onderstepoort stain of CDV which infects these cells giving extensive cell fusion after 2 days in a similar manner to vaccine strains of MV. The Onderstepoort virus is therefore likely to use an unknown high density receptor in Vero but it cannot be ruled out that proHB-EGF could also be utilised. ProHB-EGF has been identified as the diphtheria toxin receptor and although the phocine sequence is unknown other members of the carnivore show 89% identity with the human and monkey amino acid sequence. Furthermore, juxtamembrane and transmembrane domains, as well as a proposed heparin-binding region are highly conserved across these species which would explain the lack of adaption required by wtPDV to use the receptor in Vero cells. Although proHB-EGF is expressed in all mammalian species examined to date, species differences in the DT binding site and hence sensitivity to this toxin occur. Vero cells are extremely sensitive to DT whereas mouse and rat cells are resistant. Hamster cells demonstrate intermediate sensitivity. Our results show that wtPDV can bind 20 times more efficiently to Vero than to CHO cells, suggesting that the virus may be binding to the DT binding site but this will require investigation. It has been reported that gut epithelium is extensively infected by PDV in harbour seals whereas in experimental CDV infection of this species the evidence for infection in epithelial is inconclusive. This could be explained by the ability of PDV but not CDV to ustilise phocine proHB-EGF.