Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
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DOI：
10.1084/jem.20110363
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发表时间：
2011-10-24
期刊：
影响因子：
--
通讯作者：
Haynes BF
中科院分区：
文献类型：
--
作者：
Liao HX;Chen X;Munshaw S;Zhang R;Marshall DJ;Vandergrift N;Whitesides JF;Lu X;Yu JS;Hwang KK;Gao F;Markowitz M;Heath SL;Bar KJ;Goepfert PA;Montefiori DC;Shaw GC;Alam SM;Margolis DM;Denny TN;Boyd SD;Marshal E;Egholm M;Simen BB;Hanczaruk B;Fire AZ;Voss G;Kelsoe G;Tomaras GD;Moody MA;Kepler TB;Haynes BF
HIV-1传播后不久，许多HIV-1病毒反应性抗体可能来自先前由非HIV-1宿主或微生物抗原刺激的群反应性记忆B细胞。对HIV-1的初始抗体反应靶向包膜（Env）gp 41，并且是非中和性的，在控制病毒血症方面无效。为了了解HIV-1传播后不久产生的gp 41结合抗体的起源和特征，我们从急性感染HIV-1的受试者中分离并研究了gp 41反应性浆细胞。在这些gp 41反应性抗体中，体细胞突变的频率相对较高。来自HIV-1急性感染受试者的gp 41反应性抗体的回复未突变祖先通常不与自体HIV-1 Env反应;然而，这些抗体是多反应性的，并且经常与宿主或细菌抗原结合。在gp 41反应性抗体的一个大的克隆谱系中，对HIV-1 Env的反应性仅在体细胞突变后获得。多反应性gp 41结合抗体也从未感染个体中分离。这些数据表明，急性HIV-1感染后产生的大多数gp 41结合抗体是通过刺激先前已被非HIV-1抗原激活的记忆B细胞产生的交叉反应性应答。
Many HIV-1 envelope-reactive antibodies shortly after HIV-1 transmission may arise from crow-reactive memory B cells previously stimulated by non-HIV-1 host or microbial antigens The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non–HIV-1 antigens.
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影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
影响因子：
5.4
作者：
CHIN, LT;MALMBORG, AC;BORREBAECK, CAK
通讯作者：
BORREBAECK, CAK
影响因子：
56.9
作者：
BERBERIAN, L;GOODGLICK, L;BRAUN, J
通讯作者：
BRAUN, J
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.
影响因子：
17.1
作者：
Boyd SD;Marshall EL;Merker JD;Maniar JM;Zhang LN;Sahaf B;Jones CD;Simen BB;Hanczaruk B;Nguyen KD;Nadeau KC;Egholm M;Miklos DB;Zehnder JL;Fire AZ
通讯作者：
Fire AZ