NEUTRALIZATION SENSITIVITY AND ACCESSIBILITY OF CONTINUOUS B-CELL EPITOPES OF THE FELINE IMMUNODEFICIENCY VIRUS ENVELOPE

Antibodies elicited during natural infection of domestic cats by the f eline immunodeficiency virus (FIV) recognize continuous epitopes in ni ne domains of the virus envelope glycoproteins. Whereas antibodies dir ected against the V3 envelope region can neutralize laboratory-adapted virus, neutralization of FIV has been shown to depend upon cellular s ubstrate, and virus adaptation to laboratory cell lines may alter sens itivity to neutralizing antibodies. We therefore undertook a systemati c analysis of the continuous B cell epitopes of the envelope of a prim ary FIV isolate, Wo. The capacity of feline antisera elicited against nine envelope domains to neutralize primary and laboratory-adapted vir us was evaluated in feline peripheral blood mononuclear cells (PBMC). The laboratory-adapted strain Petaluma was used to compare neutralizat ion in PBMC and Crandell feline kidney cells (CrFK). Antibodies specif ic for the V3 region neutralized both primary and laboratory-adapted v irus whether residual infectivity was measured in CrFK or in feline PB MC. However, a large discrepancy in the efficiency of neutralization w as observed in these ex vivo models of infection, perhaps reflecting d iversity in the interaction between virus and different cellular targe ts. We also examined the accessibility of epitopes on the functional o ligomeric envelope complex of FIV. Most of the epitopes were poorly ex posed on native envelope glycoproteins at the surface of live infected cells. The most accessible domain was the only domain sensitive to ne utralizing antibodies. These results suggest that inaccessibility on o ligomeric envelope glycoproteins may frequently underlie the insensiti vity of diverse lentivirus B cell epitopes to neutralization.