ObjectiveFine mapping of HIV-1 gp41 fusion-critical sites.Design and methodsAntibodies 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.ResultsThis 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.ConclusionsThis 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.