<p>HIV-1 envelope conformational changes necessary for viral infection make the gp41 subunit a key target for antiviral drugs. Using reverse vaccinology applied to a mucosal HIV-1 neutralizing IgA, we identified P7, a 12 amino-acid peptide at the interface of the N and C-helices of gp41. We now show that P7 interacts with the trimeric HIV-1 envelope cross-clade with a nanomolar affinity, captures gp41 in a 6-Helix Bundle conformation, and binds to infected cells and free virus. Functionally, P7 neutralizes HIV infection cross-clade and inhibits cell-to-cell viral transfer. Adding a lipid tail to P7 (Lipo-P7) improved neutralization of primary CD4<sup>+</sup> T cells by Transmitted / Founder clade B and primary clades A and C viruses. Lipo-P7 also neutralized a T20-resistant virus harboring gp41 G36D, V38M mutations. Altogether, P7 appears as a promising cross-clade HIV-1 antiviral peptide that could also induce protective mucosal IgA levels to prevent sexual HIV infection.</p>

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The conformational epitope of a gp41-specific mucosal protective IgA binds to the HIV-1 envelope and neutralizes infection

  • Inès Sahnoune,
  • Andréa Cottignies-Calamarte,
  • Annouk Dauvilliers,
  • Kingsley Essemiah,
  • Tahar Bouceba,
  • Christophe Piesse,
  • Daniela Tudor,
  • Morgane Bomsel

摘要

HIV-1 envelope conformational changes necessary for viral infection make the gp41 subunit a key target for antiviral drugs. Using reverse vaccinology applied to a mucosal HIV-1 neutralizing IgA, we identified P7, a 12 amino-acid peptide at the interface of the N and C-helices of gp41. We now show that P7 interacts with the trimeric HIV-1 envelope cross-clade with a nanomolar affinity, captures gp41 in a 6-Helix Bundle conformation, and binds to infected cells and free virus. Functionally, P7 neutralizes HIV infection cross-clade and inhibits cell-to-cell viral transfer. Adding a lipid tail to P7 (Lipo-P7) improved neutralization of primary CD4+ T cells by Transmitted / Founder clade B and primary clades A and C viruses. Lipo-P7 also neutralized a T20-resistant virus harboring gp41 G36D, V38M mutations. Altogether, P7 appears as a promising cross-clade HIV-1 antiviral peptide that could also induce protective mucosal IgA levels to prevent sexual HIV infection.