Predominant envelope variable loop 2-specific and gp120-specific antibody-dependent cellular cytotoxicity antibody responses in acutely SIV-infected African green monkeys.
Predominant envelope variable loop 2-specific and gp120-specific antibody-dependent cellular cytotoxicity antibody responses in acutely SIV-infected African green monkeys.
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DOI：
10.1186/s12977-018-0406-5
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发表时间：
2018-03-09
期刊：
影响因子：
3.3
通讯作者：
Permar SR
中科院分区：
文献类型：
--
作者：
Nguyen QN;Martinez DR;Himes JE;Whitney Edwards R;Han Q;Kumar A;Mangan R;Nicely NI;Xie G;Vandergrift N;Shen X;Pollara J;Permar SR
在急性HIV-1感染者和猴免疫缺陷病毒(SIV)感染的恒河猴(RMS)中，初始包膜(Env)特异性抗体反应主要由针对Env gp41的非中和抗体主导。相比之下，自然灵长类SIV宿主，如非洲绿猴(AGM)，对SIV感染产生主要的Env gp120特异性抗体反应。然而，SIV环境特异性血浆免疫球蛋白的精细表位特异性和功能，以及它们在SIV感染的AGM和RMS中对自体病毒协同进化的潜在作用仍不清楚。与RMS中主要的线性gp41特异性免疫球蛋白反应不同，SIV感染的AGM在急性感染期间表现出独特的线性可变环2(V2)特异性血浆免疫球蛋白应答，该应答与高gp120直接抗体依赖的细胞毒(ADCC)活性和SIVsab感染的细胞结合反应同时出现。此外，与RMS相比，从SIV感染的AGM中分离的SIV变异株在Env V1V2环内显示出更高的氨基酸突变频率。值得注意的是，AGM中的线性V2特异性免疫球蛋白表位与HIV V2环的一个类似区域重叠，该区域包含在RV144疫苗接种者的突破性病毒中发现的K169突变表位。疫苗激发的环境病毒V2特异性免疫球蛋白应答被认为是降低人类和RMS感染HIV-1/SIV风险的免疫相关因素。然而，激发这些具有潜在保护性的V2特异性免疫球蛋白的途径仍不清楚。在这项研究中，我们证明了SIV感染的AGM是SIV的自然宿主，在SIV环境gp120介导的ADCC介导的同时，SIV感染的AGM表现出高的血浆线性V2特异性的Ig G结合反应，以及SIV感染的细胞血浆Ig G结合反应，这在SIV急性感染的RMS中是不存在的。AGM中的线性V2特异性抗体反应针对的是中等保护性RV144 HIV-1疫苗试验中定义的疫苗诱导免疫压力的建议部位的重叠表位。在这些自然SIV宿主中识别控制早期激发Env V2特异性Ig G和ADCC抗体反应的宿主因素，可以为旨在快速诱导潜在保护性HIV-1 Env特异性反应的疫苗接种策略提供依据。本文的在线版本(10.1186/s12977-0180406-5)包含补充材料，可供授权用户使用。
The initial envelope (Env)-specific antibody response in acutely HIV-1-infected individuals and simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs) is dominated by non-neutralizing antibodies targeting Env gp41. In contrast, natural primate SIV hosts, such as African green monkeys (AGMs), develop a predominant Env gp120-specific antibody response to SIV infection. However, the fine-epitope specificity and function of SIV Env-specific plasma IgG, and their potential role on autologous virus co-evolution in SIV-infected AGMs and RMs remain unclear. Unlike the dominant linear gp41-specific IgG responses in RMs, SIV-infected AGMs demonstrated a unique linear variable loop 2 (V2)-specific plasma IgG response that arose concurrently with high gp120-directed antibody-dependent cellular cytotoxicity (ADCC) activity, and SIVsab-infected cell binding responses during acute infection. Moreover, SIV variants isolated from SIV-infected AGMs exhibited high amino acid mutation frequencies within the Env V1V2 loop compared to those of RMs. Notably, the linear V2-specific IgG epitope in AGMs overlaps with an analogous region of the HIV V2 loop containing the K169 mutation epitope identified in breakthrough viruses from RV144 vaccinees. Vaccine-elicited Env V2-specific IgG responses have been proposed as an immune correlate of reduced risk in HIV-1/SIV acquisition in humans and RMs. Yet the pathways to elicit these potentially-protective V2-specific IgG responses remain unclear. In this study, we demonstrate that SIV-infected AGMs, which are the natural hosts of SIV, exhibited high plasma linear V2-specific IgG binding responses that arose concurrently with SIV Env gp120-directed ADCC-mediating, and SIV-infected cell plasma IgG binding responses during acute SIV infection, which were not present in acutely SIV-infected RMs. The linear V2-specific antibody response in AGMs targets an overlapping epitope of the proposed site of vaccine-induced immune pressure defined in the moderately protective RV144 HIV-1 vaccine trial. Identifying host factors that control the early elicitation of Env V2-specific IgG and ADCC antibody responses in these natural SIV hosts could inform vaccination strategies aimed at rapidly inducing potentially-protective HIV-1 Env-specific responses in humans. The online version of this article (10.1186/s12977-018-0406-5) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Edmonds TG;Ding H;Yuan X;Wei Q;Smith KS;Conway JA;Wieczorek L;Brown B;Polonis V;West JT;Montefiori DC;Kappes JC;Ochsenbauer C
通讯作者：
Ochsenbauer C
DOI：
10.1097/qai.0000000000000530
发表时间：
2015-04-15
影响因子：
3.6
作者：
Guo, Jia;Zuo, Teng;Chen, Zhiwei
通讯作者：
Chen, Zhiwei
影响因子：
20.3
作者：
Brenchley, Jason M.;Vinton, Carol;Estes, Jacob D.
通讯作者：
Estes, Jacob D.
影响因子：
5.4
作者：
Gnanadurai, Clement Wesley;Pandrea, Ivona;Kirchhoff, Frank
通讯作者：
Kirchhoff, Frank
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH