Intriguing interplay between feline infectious peritonitis virus and its receptors during entry in primary feline monocytes

Two potential receptors have been described for the feline infectious peritonitis virus (FIPV): feline aminopeptidase N (fAPN) and feline dendritic cell-specific intercellular adhesion molecule grabbing non-integrin (fDC-SIGN). In cell lines, fAPN serves as a receptor for serotype II, but not for serotype I FIPV. The role of fAPN in infection of in vivo target cells, monocytes, is not yet confirmed. Both serotype I and II FIPVs use fDC-SIGN for infection of monocyte-derived cells but how is not known. In this study, the role of fAPN and fDC-SIGN was studied at different stages in FIPV infection of monocytes. First, the effects of blocking the potential receptor(s) were studied for the processes of attachment and infection. Secondly, the level of co-localization of FIPV and the receptors was determined. It was found that FIPV I binding and infection were not affected by blocking fAPN while blocking fDC-SIGN reduced FIPV I binding to 36% and practically completely inhibited infection. Accordingly, 66% of bound FIPV I particles co-localized with fDC-SIGN. Blocking fAPN reduced FIPV II binding by 53% and infection by 80%. Further, 60% of bound FIPV II co-localized with fAPN. fDC-SIGN was not involved in FIPV II binding but infection was reduced with 64% when fDC-SIGN was blocked. In conclusion, FIPV I infection of monocytes depends on fDC-SIGN. Most FIPV I particles already interact with fDC-SIGN at the plasma membrane. For FIPV II, both fAPN and fDC-SIGN are involved in infection with only fAPN playing a receptor role at the plasma membrane.