Discrete regions of HIV-1 gp41 defined by syncytia-inhibiting affinity-purified human antibodies.
OBJECTIVE
Fine mapping of HIV-1 gp41 fusion-critical sites.


METHODS
Antibodies from human HIV-1-positive sera were affinity-purified on a panel of synthetic overlapping peptides spanning residues 526-682 of the extracellular portion of HIV-1 gp41. The syncytium-inhibiting capacity of the immunopurified antibodies and their differential reactivity on the synthetic peptides were tested.


RESULTS
This approach enabled the identification of residues 583-591 (ARILAVERY), 595-599 (QQLLG), 603-609 (CSGKLIC) and 664-673 (ELLELDKWAS) as possibly involved in the fusion process. Reduction in the anti-ARILAVERY, anti-CSGKLIC and anti-ELLELDKWAS antibody titres and frequencies correlates with disease progression. Syncytia-inhibition capacity of sera did not correlate with the presence of high-titre antibodies reacting with any of the peptides tested, suggesting that most fusion-affecting antibodies are not directed towards gp41.


CONCLUSIONS
This strategy may be relevant for understanding the contribution of anti-gp41 antibodies in protecting against the pathogenic effects of the virus and in the design of an effective env vaccine.
Vanini
S
S
Dipartimento di Biologia e Tecnologia, H. San Raffaele, CNR Istituto di Chimica degli Ormoni, Milan, Italy.
Longhi
R
R
Lazzarin
A
A
Vigo
E
E
Siccardi
A G
AG
Viale
G
G
D000595:Amino Acid Sequence; D002459:Cell Fusion / Q000276:immunology; D002460:Cell Line; D002846:Chromatography, Affinity; D000939:Epitopes / Q000235:genetics; D015483:HIV Antibodies / Q000302:isolation & purification; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010455:Peptides; D014760:Viral Fusion Proteins