Characterization of a trimeric MPER containing HIV-1 gp41 antigen

Characterization of a trimeric MPER containing HIV-1 gp41 antigen
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DOI:
10.1016/j.virol.2009.05.015
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发表时间:
2009-08-01
期刊:
影响因子:
3.7
通讯作者:
Weissenhorn, Winfried
Weissenhorn, Winfried
中科院分区:
医学3区
文献类型:
--
作者:
Hinz, Andreas;Schoehn, Guy;Weissenhorn, Winfried

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gp41 的近膜外部区域 (MPER) 被认为是诱导中和抗体的主要靶标,因为它包含三种广泛中和抗体(2F5、4E10 和 Z13)的表位。在这里,我们提出了一种新型 gp41 构建体(HA-gp41),包含两端融合到两个三链卷曲螺旋结构域的 gp41 HR2 和 MPER。 HA-gp41 是三聚体,在溶液中具有高螺旋含量,并通过负染色电子显微镜显示形成棒状结构。用 HA-gp41 免疫兔子诱导了针对 MPER 的抗体,该抗体未能对初级分离株的包膜发挥显着的中和能力。因此,MPER 区域的三聚化不足以诱导对 gp41 内保守区域特异的有效中和抗体反应。 (C) 2009 Elsevier Inc. 保留所有权利。
The membrane-proximal external region (MPER) of gp41 is considered as a prime target for the induction of neutralizing antibodies, since it contains the epitopes for three broadly neutralizing antibodies (2F5, 4E10 and Z13). Here we present a novel gp41 construct (HA-gp41) comprising gp41 HR2 and MPER fused to two triple-stranded coiled-coil domains at both ends. HA-gp41 is trimeric, has a high helical content in solution and forms rod-like structures as revealed by negative staining electron microscopy. Immunization of rabbits with HA-gp41 induced antibodies directed against MPER, which failed to exert significant neutralization capacity against envelopes from primary isolates. Thus trimerisation of MPER regions does not suffice to induce a potent neutralizing antibody response specific for conserved regions within gp41. (C) 2009 Elsevier Inc. All rights reserved.