Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms.
Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms.
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DOI：
10.1016/j.virol.2010.02.029
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发表时间：
2010-06-05
期刊：
影响因子：
3.7
通讯作者：
Sullivan NJ
中科院分区：
文献类型：
--
作者：
Shedlock DJ;Bailey MA;Popernack PM;Cunningham JM;Burton DR;Sullivan NJ
人类埃博拉病毒引起严重的出血热疾病，死亡率高，没有疫苗或治疗方法。幸存者体内的抗体出现较早，持续存在，并且在转移到非人灵长类动物体内时可以延迟感染。来自幸存者的单克隆抗体（mab）在体外表现出强大的中和活性，并对啮齿动物具有保护作用。为了更好地了解中和的靶标和机制，我们研究了一组单克隆抗体，这些单克隆抗体先前显示与包膜糖蛋白（GP）发生反应。虽然一个非中和的单抗识别非必需黏液样结构域的GP表位，但其余的单抗是GP1特异性的，是中和的，并且可以通过与分泌的GP的反应性进一步区分。我们发现幸存者抗体，人类KZ52和猴子JP3K11，对GP1和GP2残基构成的构象依赖性表位具有特异性，并且通过两种不同的机制发生中和；KZ52抑制组织蛋白酶对GP的切割，而JP3K11识别裂解的融合活性形式的GP。
Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.
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影响因子：
6.7
作者：
Oswald, Wendelien B;Geisbert, Thomas W;Davis, Kelly J;Geisbert, Joan B;Sullivan, Nancy J;Jahrling, Peter B;Parren, Paul W H I;Burton, Dennis R
通讯作者：
Burton, Dennis R
DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
通讯作者：
Choe H
影响因子：
5.4
作者：
Maruyama, T;Rodriguez, LL;Burton, DR
通讯作者：
Burton, DR
影响因子：
3.7
作者：
Pager, CT;Craft, WW;Dutch, RE
通讯作者：
Dutch, RE
影响因子：
5.4
作者：
Gupta, M;Mahanty, S;Rollin, PE
通讯作者：
Rollin, PE