A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope.
A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope.
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DOI：
10.1016/j.immuni.2018.02.013
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发表时间：
2018-03-20
期刊：
影响因子：
32.4
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Zhou T;Zheng A;Baxa U;Chuang GY;Georgiev IS;Kong R;O'Dell S;Shahzad-Ul-Hussan S;Shen CH;Tsybovsky Y;Bailer RT;Gift SK;Louder MK;McKee K;Rawi R;Stevenson CH;Stewart-Jones GBE;Taft JD;Waltari E;Yang Y;Zhang B;Shivatare SS;Shivatare VS;Lee CD;Wu CY;NISC Comparative Sequencing Program;Mullikin JC;Bewley CA;Burton DR;Polonis VR;Shapiro L;Wong CH;Mascola JR;Kwong PD;Wu X
事实上，HIV-1包膜三聚体的整个表面都被中和抗体识别，除了gp 120亚基上“沉默面”中心的高度糖基化区域。从HIV-1感染的供体#74中，我们鉴定出抗体VRC-PG 05，其中和27%的HIV-1菌株。与gp 120复合的VRC-PG 05的抗原结合片段的共晶体结构揭示了在沉默面中心主要由来自N262、N295和N448的N-连接聚糖组成的表位。体细胞超突变优先发生在与这些聚糖相互作用的抗体残基处，表明聚糖识别的体细胞发育。供体#74对VRC-PG 05的耐药性涉及聚糖-N448至N446的移位或聚糖近端残基E293的突变。因此，HIV-1中和可以通过聚糖识别抗体在沉默面中心实现;沿着其他已知表位，VRC-PG 05表位通过中和抗体完全覆盖融合前封闭三聚体的所有主要暴露区域。HIV-1包膜上“沉默的面孔”的中心被聚糖屏蔽，没有抗体识别。Zhou等人鉴定了抗体VRC-PG 05，其在沉默面中心结合聚糖主导的表位，并完成包膜三聚体的所有主要暴露区域的抗体识别。
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 co-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. The center of the “silent face” on the HIV-1 envelope is shielded by glycans and has been devoid of antibody recognition. Zhou et al. identify the antibody VRC-PG05, which binds a glycan-dominated epitope at the silent face center and completes antibody recognition of all major exposed regions of the envelope trimer.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
2.9
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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