Discrete regions of HIV-1 gp41 defined by syncytia-inhibiting affinity-purified human antibodies

OBJECTIVE: Fine mapping of HIV-1 gp41 fusion-critical sites. DESIGN AND 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.