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1 Génétique des Virus (ICGM-CNRS UPR 0415), Institut Cochin de Génétique Moléculaire, 22 rue Méchain, 75014 Paris
and2 Génétique moléculaire génétique virale Institut National de la Recherche Agronomique, Ecole Nationale Vétérinaire d'Alfort, 947094 Maisons-Alfort Cedex, France
Antibodies elicited during natural infection of domestic cats by the feline immunodeficiency virus (FIV) recognize continuous epitopes in nine domains of the virus envelope glycoproteins. Whereas antibodies directed against the V3 envelope region can neutralize laboratory-adapted virus, neutralization of FIV has been shown to depend upon cellular substrate, and virus adaptation to laboratory cell lines may alter sensitivity to neutralizing antibodies. We therefore undertook a systematic analysis of the continuous B cell epitopes of the envelope of a primary FIV isolate, Wo. The capacity of feline antisera elicited against nine envelope domains to neutralize primary and laboratory-adapted virus was evaluated in feline peripheral blood mononuclear cells (PBMC). The laboratory-adapted strain Petaluma was used to compare neutralization in PBMC and Crandell feline kidney cells (CrFK). Antibodies specific for the V3 region neutralized both primary and laboratory-adapted virus whether residual infectivity was measured in CrFK or in feline PBMC. However, a large discrepancy in the efficiency of neutralization was observed in these ex vivo models of infection, perhaps reflecting diversity in the interaction between virus and different cellular targets. We also examined the accessibility of epitopes on the functional oligomeric envelope complex of FIV. Most of the epitopes were poorly exposed on native envelope glycoproteins at the surface of live infected cells. The most accessible domain was the only domain sensitive to neutralizing antibodies. These results suggest that inaccessibility on oligomeric envelope glycoproteins may frequently underlie the insensitivity of diverse lentivirus B cell epitopes to neutralization.
Present address: Department of Microbiology, H-325 Health Sciences Center, SC-42, Seattle, WA 98195, USA
* Author for correspondence. Fax +33 1 40 51 72 10. e-mail pancino@cochin.inserm.fr
Received 7 September 1995;
accepted 14 November 1995.
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