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A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope

2018; Cell Press; Volume: 48; Issue: 3 Linguagem: Inglês

10.1016/j.immuni.2018.02.013

1097-4180

Tongqing Zhou, Anqi Zheng, Ulrich Baxa, Gwo‐Yu Chuang, Ivelin S. Georgiev, Rui Kong, Sijy O’Dell, Syed Shahzad‐ul‐Hussan, Chen‐Hsiang Shen, Yaroslav Tsybovsky, Robert T. Bailer, Syna Kuriakose Gift, Mark K. Louder, Krisha McKee, Reda Rawi, Catherine Stevenson, Guillaume B. E. Stewart-Jones, Justin Taft, Eric Waltari, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang‐Chun D. Lee, Chung‐Yi Wu, James C. Mullikin, Carole A. Bewley, Dennis R. Burton, Victoria R. Polonis, Lawrence Shapiro, Chi‐Huey Wong, John R. Mascola, Peter D. Kwong, Xueling Wu, Betty Benjamin, Robert W. Blakesley, Gerry Bouffard, Shelise Brooks, Holly Coleman, Mila Dekhtyar, Michael Gregory, Xiaobin Guan, Jyoti Gupta, Joel Han, April Hargrove, Shi-ling Ho, Richelle Legaspi, Quino Maduro, Cathy Masiello, Baishali Maskeri, Jenny McDowell, Casandra Montemayor, James C. Mullikin, Morgan Park, Nancy L. Riebow, Karen Schandler, Brian Schmidt, Christina Sison, Mal Stantripop, James W. Thomas, Pam Thomas, Meg Vemulapalli, Alice Young,

Glycosylation and Glycoproteins Research

Virtually the entire surface of the HIV-1-envelope trimer is recognized by neutralizing antibodies, except for a highly glycosylated region at the center of the “silent face” on the gp120 subunit. From an HIV-1-infected donor, #74, we identified antibody VRC-PG05, which neutralized 27% of HIV-1 strains. The crystal structure of the antigen-binding fragment of VRC-PG05 in complex with gp120 revealed an epitope comprised primarily of N-linked glycans from N262, N295, and N448 at the silent face center. Somatic hypermutation occurred preferentially at antibody residues that interacted with these glycans, suggesting somatic development of glycan recognition. Resistance to VRC-PG05 in donor #74 involved shifting of glycan-N448 to N446 or mutation of glycan-proximal residue E293. HIV-1 neutralization can thus be achieved at the silent face center by glycan-recognizing antibody; along with other known epitopes, the VRC-PG05 epitope completes coverage by neutralizing antibody of all major exposed regions of the prefusion closed trimer.