Neutralization of feline immunodeficiency virus by antibodies targeting the V5 loop of Env.
Neutralizing antibodies (NAbs) play a vital role in vaccine-induced protection against infection with feline immunodeficiency virus (FIV). However, little is known about the appropriate presentation of neutralization epitopes in order to induce NAbs effectively; the majority of the antibodies that are induced are directed against non-neutralizing epitopes. Here, we demonstrate that a subtype B strain of FIV, designated NG4, escapes autologous NAbs, but may be rendered neutralization-sensitive following the insertion of two amino acids, KT, at positions 556-557 in the fifth hypervariable (V5) loop of the envelope glycoprotein. Consistent with the contribution of this motif to virus neutralization, an additional three subtype B strains retaining both residues at the same position were also neutralized by the NG4 serum, and serum from an unrelated cat (TOT1) targeted the same sequence in V5. Moreover, when the V5 loop of subtype B isolate KNG2, an isolate that was moderately resistant to neutralization by NG4 serum, was mutated to incorporate the KT motif, the virus was rendered sensitive to neutralization. These data suggest that, even in a polyclonal serum derived from FIV-infected cats following natural infection, the primary determinant of virus-neutralizing activity may be represented by a single, dominant epitope in V5.
Samman
Ayman
A
Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden, Glasgow G61 1QH, UK.
Logan
Nicola
N
McMonagle
Elizabeth L
EL
Ishida
Takuo
T
Mochizuki
Masami
M
Willett
Brian J
BJ
Hosie
Margaret J
MJ
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002415:Cats; D016000:Cluster Analysis; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins