Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses.
Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses.
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DOI：
10.1016/j.chom.2015.11.005
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发表时间：
2015-12-09
影响因子：
30.3
通讯作者：
Abraham J
中科院分区：
文献类型：
--
作者：
Mahmutovic S;Clark L;Levis SC;Briggiler AM;Enria DA;Harrison SC;Abraham J
在西半球，至少有五种乳头状病毒引起人类病毒性出血热，死亡率很高。Junín病毒（JUNV）是唯一一种将含有中和抗体（“被动免疫”）的幸存者免疫血浆输注为既定治疗方法的出血热病毒。在这里，我们报道了JUNV表面糖蛋白受体结合亚基（GP1）与中和单克隆抗体结合的结构。该抗体结合转铁蛋白受体1 （TfR1）的GP1位点，并模拟重要的受体接触。转铁蛋白受体1是所有新世界出血热乳头状病毒的宿主细胞表面受体。我们发现幸存者免疫血浆中含有结合相同表位的抗体。我们认为病毒受体结合位点的可达性解释了对JUNV被动免疫的成功，并且这种功能保守的表位是限制所有新世界出血热乳头状病毒感染的治疗和疫苗的潜在靶点。
In the Western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. Junín virus (JUNV) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies (‘passive immunity’) is an established treatment. Here, we report the structure of the JUNV surface glycoprotein receptor-binding subunit (GP1) bound to a neutralizing monoclonal antibody. The antibody engages the GP1 site that binds transferrin receptor 1 (TfR1) – the host cell surface receptor for all New World hemorrhagic fever mammarenaviruses - and mimics an important receptor contact. We show that survivor immune plasma contains antibodies that bind the same epitope. We propose that viral receptor-binding site accessibility explains the success of passive immunity against JUNV and that this functionally conserved epitope is a potential target for therapeutics and vaccines to limit infection by all New World hemorrhagic fever mammarenaviruses.