Most Potential Linear B Cell Epitopes of Env Glycoproteins of Feline Immunodeficiency Virus Are Immunogenically Silent in Infected Cats

Abstract

A battery of sixty-six 20- to 23-amino acid synthetic peptides, partially overlapping by 10-12 amino acids, spanning the entire sequence of the envelope (Env) glycoproteins of the Petaluma isolate of feline immunodeficiency virus (FIV-Pet), has been used to map Env linear B cell epitopes. By screening FIV-infected cat sera for anti-peptide reactivity, the existence of two immunodominat domains, namely the V3 region of the surface (SU) glycoprotein and the domain including the highly conserved sequence QNQFF of the transmembrane (TM) glycoprotein, was detected; antibody-binding sites were also mapped in the domain overlapping the cleavage site between SU and TM encompassing the V6 variable region. Moreover, at least two novel linear B epitopes, the former spanning residues 427M-H446 and the latter spanning residues 737N-N756 and likely representing a "type-specific" determinant, have been revealed. The battery of synthetic peptides was then used to immunize outbred Swiss mice in the attempt to reveal other potential sites of immunogenicity of the Env glycoproteins. Analysis of peptide-immunized mouse sera for anti-peptide reactivity revealed more numerous B cell epitopes, generally mapping in different peptides, as compared with those defined in the feline system. None of the mouse anti-peptide sera, however, proved neutralizing for FIV-Pet.

Antibodies Generated in Cats by a Lipopeptide Reproducing the Membrane-Proximal External Region of the Feline Immunodeficiency Virus Transmembrane Enhance Virus Infectivity

“…In contrast, four FIV-Pet-infected cat sera and two FIV-M2-infected cat sera bound lipo-P59 regardless of whether this was mixed with MLM but not P59. On the other hand, the reactivities of the infected cat sera to the other peptides in the panel were in agreement with the fact that the FIV TrpM is totally silent in the course of infection (12,32): in particular, confirming previous findings (12), these sera bound the peptides L36I (13/13 cats) and E29K (5/13 cats) but were completely unreactive to Map-C8. Enhancement of FIV infection but no neutralization with lipo-P59 antibodies.…”

“…Whatever the mechanism, the finding has revealed for the first time that the MPER of the FIV TM contains at least one epitope potentially capable of inducing virus-enhancing antibodies and that this epitope is also expressed by a properly presented MPER-reproducing oligopeptide. In contrast, putative neutralizing epitopes present in the MPER of FIV have to date proven difficult to mimic using the oligopeptide approach (1,8,12,32,39,46). It is noteworthy that the MPER in the TM of HIV-1 also is poorly immunogenic during virus infection and that although this structure contains well-conserved epitopes recognized by a few neutralizing human monoclonal antibodies (57), all efforts to generate neutralizing antibodies with a variety of linear or structurally constrained MPER peptides, used as such or within different protein scaffolds or virus-like particles, have so far failed (25,27).…”

Antiviral Activity and Conformational Features of an Octapeptide Derived from the Membrane-Proximal Ectodomain of the Feline Immunodeficiency Virus Transmembrane Glycoprotein

“…Unfortunately, antibodies reactive with this region are very infrequent in HIV-1 patients and have never been elicited with candidate vaccines, so far (69). In our hands, the corresponding domain of FIV is also poorly immunogenic, as determined in infected cats and in mice repeatedly injected with derived peptides (41). However, groups using other strains of FIV have shown that the same domain is widely recognized by infected cat sera and also immunogenic when presented to cats as a fusion protein (14,52).…”

Sequential CD134-CXCR4 Interactions in Feline Immunodeficiency Virus (FIV): Soluble CD134 Activates FIV Env for CXCR4-Dependent Entry and Reveals a Cryptic Neutralization Epitope

“…However, anti-V3 monospecific sera and monoclonal antibody (MAb) elicited against V3 peptides only weakly neutralize virus infection (7, 13, 14, 16-19, 22, 23, 25), and V3 monospecific sera or monoclonal antibodies poorly recognize V3 on the mature Env oligomer (19,22). Thus, V3 may be inaccessible due to masking by carbohydrates and/or tertiary or quaternary interactions within the Env oligomeric complex.…”