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


ABSTRACT: 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.

SUBMITTER: Zhou T 

PROVIDER: S-EPMC6421865 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Zhou Tongqing T   Zheng Anqi A   Baxa Ulrich U   Chuang Gwo-Yu GY   Georgiev Ivelin S IS   Kong Rui R   O'Dell Sijy S   Shahzad-Ul-Hussan Syed S   Shen Chen-Hsiang CH   Tsybovsky Yaroslav Y   Bailer Robert T RT   Gift Syna K SK   Louder Mark K MK   McKee Krisha K   Rawi Reda R   Stevenson Catherine H CH   Stewart-Jones Guillaume B E GBE   Taft Justin D JD   Waltari Eric E   Yang Yongping Y   Zhang Baoshan B   Shivatare Sachin S SS   Shivatare Vidya S VS   Lee Chang-Chun D CD   Wu Chung-Yi CY   Mullikin James C JC   Bewley Carole A CA   Burton Dennis R DR   Polonis Victoria R VR   Shapiro Lawrence L   Wong Chi-Huey CH   Mascola John R JR   Kwong Peter D PD   Wu Xueling X  

Immunity 20180313 3


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 ce  ...[more]

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