Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers.
Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers.
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DOI：
10.3389/fimmu.2021.670561
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发表时间：
2021
影响因子：
7.3
通讯作者：
Tomaras GD
中科院分区：
文献类型：
--
作者：
Nyanhete TE;Edwards RJ;LaBranche CC;Mansouri K;Eaton A;Dennison SM;Saunders KO;Goodman D;Janowska K;Spreng RL;Zhang L;Mudrak SV;Hope TJ;Hora B;Bradley T;Georgiev IS;Montefiori DC;Acharya P;Tomaras GD
广谱中和抗体(BNAbs)是已知的介导HIV-1感染的免疫控制的抗体，只在一小部分HIV-1感染者中产生。尽管bNAbs传统上与高病毒载量的患者有关，但在自然控制病毒复制的单纯HIV-1+患者的治疗中也观察到了bNAbs[病毒控制器(VC)]。因此，剖析VCs中的bNAb反应将提供关于什么构成对自然HIV-1感染的有效体液反应的关键信息。在这项研究中，我们确定了针对HIV-1自然感染的多克隆bNAb反应，靶向是HIV-1包膜(Env)上的CD4结合位点(CD4bs)、V3-多糖、gp120-gp41界面和膜-近端外区(MPER)表位。多克隆抗病毒抗体(Ab)反应还包括抗体依赖的细胞吞噬AE、B和C分支病毒，与Fv和Fc结构域的功能一致。序列分析显示，来自其中一个VC的env的特征与潜在的免疫压力和病毒对靶向bNAbs的V3-葡聚糖的逃逸一致。具有bNAb活性的VCs中多克隆bNAb反应的表位图谱突出了gp120-gp41界面和CD4b抗体类别的存在，这些抗体与已知的有效bNAb具有相似的结合谱。因此，这些发现揭示了VCs对自然HIV-1感染的广泛和多功能体液反应的诱导。
Broadly neutralizing antibodies (bNAbs), known to mediate immune control of HIV-1 infection, only develop in a small subset of HIV-1 infected individuals. Despite being traditionally associated with patients with high viral loads, bNAbs have also been observed in therapy naïve HIV-1+ patients naturally controlling virus replication [Virus Controllers (VCs)]. Thus, dissecting the bNAb response in VCs will provide key information about what constitutes an effective humoral response to natural HIV-1 infection. In this study, we identified a polyclonal bNAb response to natural HIV-1 infection targeting CD4 binding site (CD4bs), V3-glycan, gp120-gp41 interface and membrane-proximal external region (MPER) epitopes on the HIV-1 envelope (Env). The polyclonal antiviral antibody (Ab) response also included antibody-dependent cellular phagocytosis of clade AE, B and C viruses, consistent with both the Fv and Fc domain contributing to function. Sequence analysis of envs from one of the VCs revealed features consistent with potential immune pressure and virus escape from V3-glycan targeting bNAbs. Epitope mapping of the polyclonal bNAb response in VCs with bNAb activity highlighted the presence of gp120-gp41 interface and CD4bs antibody classes with similar binding profiles to known potent bNAbs. Thus, these findings reveal the induction of a broad and polyfunctional humoral response in VCs in response to natural HIV-1 infection.
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菌株特异性和广泛中和反应之间的合作有限的病毒逃逸，并延长了广泛中和表位的暴露。
影响因子：
5.4
作者：
Anthony C;York T;Bekker V;Matten D;Selhorst P;Ferreria RC;Garrett NJ;Karim SSA;Morris L;Wood NT;Moore PL;Williamson C
通讯作者：
Williamson C
影响因子：
64.8
作者：
Caskey M;Klein F;Lorenzi JC;Seaman MS;West AP Jr;Buckley N;Kremer G;Nogueira L;Braunschweig M;Scheid JF;Horwitz JA;Shimeliovich I;Ben-Avraham S;Witmer-Pack M;Platten M;Lehmann C;Burke LA;Hawthorne T;Gorelick RJ;Walker BD;Keler T;Gulick RM;Fätkenheuer G;Schlesinger SJ;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
7.3
作者：
Hutchinson，Jennie M.;Mesa，Kathryn A.;Berman，Phillip W.
通讯作者：
Berman，Phillip W.
影响因子：
64.5
作者：
Bonsignori M;Zhou T;Sheng Z;Chen L;Gao F;Joyce MG;Ozorowski G;Chuang GY;Schramm CA;Wiehe K;Alam SM;Bradley T;Gladden MA;Hwang KK;Iyengar S;Kumar A;Lu X;Luo K;Mangiapani MC;Parks RJ;Song H;Acharya P;Bailer RT;Cao A;Druz A;Georgiev IS;Kwon YD;Louder MK;Zhang B;Zheng A;Hill BJ;Kong R;Soto C;NISC Comparative Sequencing Program;Mullikin JC;Douek DC;Montefiori DC;Moody MA;Shaw GM;Hahn BH;Kelsoe G;Hraber PT;Korber BT;Boyd SD;Fire AZ;Kepler TB;Shapiro L;Ward AB;Mascola JR;Liao HX;Kwong PD;Haynes BF
通讯作者：
Haynes BF
DOI：
10.1086/654816
发表时间：
2010-08-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Gilbert P;Wang M;Wrin T;Petropoulos C;Gurwith M;Sinangil F;D'Souza P;Rodriguez-Chavez IR;DeCamp A;Giganti M;Berman PW;Self SG;Montefiori DC
通讯作者：
Montefiori DC