Authors: R. Kong, K. Xu, T. Zhou, P. Acharya, T. Lemmin, K. Liu, G. Ozorowski, C. Soto, J. D. Taft, R. T. Bailer, E. M. Cale, L. Chen, C. W. Choi, G.-Y. Chuang, N. A. Doria-Rose, A. Druz, I. S. Georgiev, J. Gorman, J. Huang, M. G. Joyce, M. K. Louder, X. Ma, K. McKee, S. ODell, M. Pancera, Y. Yang, S. C. Blanchard, W. Mothes, D. R. Burton, W. C. Koff, M. Connors, A. B. Ward, P. D. Kwong, J. R. Mascola
Summary:
The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.
Source:
Science; 2016, 352 (6287): 828