The cross-clade neutralizing activity of a human monoclonal antibody is determined by the GPGR V3 motif of HIV type 1.
The cross-clade neutralizing activity of a human monoclonal antibody is determined by the GPGR V3 motif of HIV type 1.
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人单克隆抗体的跨进化枝中和活性由 1 型 HIV 的 GPGR V3 基序决定。
DOI：
10.1089/aid.2004.20.1254
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Gorny,MiroslawK
中科院分区：
文献类型：
--
作者：
Zolla-Pazner,Susan;Zhong,Ping;Revesz,Kathy;Volsky,Barbara;Williams,Constance;Nyambi,Phillipe;Gorny,MiroslawK
针对HIV-1 gp 120 V3结构域的多克隆和单克隆人抗体（Ab）均显示出针对原代分离株和T细胞适应病毒株的交叉进化枝中和活性。最广泛中和的人抗V3单克隆抗体（mAb）447- 52 D识别14个氨基酸，包括V3环尖端的GPxR核心表位。单克隆抗体447- 52 D中和了携带GPGR V3基序的38个原代分离株中的92%，无论病毒是否属于进化枝A、B、F或H;相反，在V3环尖端具有GPGQ和其他非GPGR/Q序列的19个病毒中没有一个对mAb 447- 52 D敏感。这些数据与mAb 447- 52 D的Fab片段与V3肽的复合物的晶体学分辨率一致，该晶体学分辨率显示mAb的结合特异性是由于识别环尖端的GPGR基序。Arg残基在该基序中的关键作用是使用病毒假型化来确定的，所述病毒假型化具有含有GPGR基序的原代分离物CA 1的包膜或具有在环的尖端处用Gln（Q）替换Arg（R）的突变包膜。虽然野生型假病毒被mAb 447- 52 D中和，但携带点突变的假病毒对中和具有抗性。这些数据阐明了广泛中和人mAb的宽度和特异性的结构基础，并有助于我们理解保护免受HIV-1感染的Ab识别的表位。
Both polyclonal and monoclonal human antibodies (Abs) to the V3 domain of HIV-1 gp120 display cross-clade neutralizing activity against primary isolates and T cell-adapted virus strains. The most broadly neutralizing of the human anti-V3 monoclonal Abs (mAbs), 447-52D, recognizes 14 amino acids, including the GPxR core epitope at the tip of the V3 loop. Monoclonal Ab 447-52D neutralized 92% of 38 primary isolates carrying the GPGR V3 motif regardless of whether the viruses belonged to clades A, B, F, or H; in contrast, none of 19 viruses with the GPGQ and other non-GPGR/Q sequences at the tip of the V3 loop was sensitive to mAb 447-52D. These data are consistent with the crystallographic resolution of a complex of the Fab fragment of mAb 447-52D with a V3 peptide that shows that the binding specificity of the mAb is due to recognition of the GPGR motif at the tip of the loop. The critical role of the Arg residue in this motif was determined using viruses pseudotyped with the envelope of primary isolate CA1 containing the GPGR motif or with a mutated envelope with a Gln (Q) replacing the Arg (R) at the tip of the loop. While the wild-type pseudovirus was neutralized by mAb 447-52D, the pseudovirus carrying the point mutation was resistant to neutralization. These data illuminate the structural basis for both the breadth and specificity of a broadly neutralizing human mAb and contribute to our understanding of the epitopes recognized by Abs that protect against infection with HIV-1.
HIV-1 中和抗性突破群体的基因型和表型特征。
DOI：
10.1006/viro.1996.0184
发表时间：
1996
期刊：
Virology.
影响因子：
--
作者：
Sirko,DA;Ehrlich,GD
通讯作者：
Ehrlich,GD
影响因子：
3.7
作者：
KELLER, PM;ARNOLD, BA;CONLEY, AJ
通讯作者：
CONLEY, AJ