Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.
Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.
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DOI：
10.1111/imr.12005
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发表时间：
2012-11
影响因子：
8.7
通讯作者：
Wilson IA
中科院分区：
文献类型：
--
作者：
Julien JP;Lee PS;Wilson IA
人类免疫缺陷病毒1型（HIV - 1）包膜蛋白（Env）和流感血凝素（HA）是负责病毒进入宿主细胞的表面糖蛋白，这是引发感染所必需的病毒生命周期的第一步。这些糖蛋白表现出高度的序列变异性和糖基化，这被用作逃避宿主免疫反应的策略。尽管如此，已经分离出对这些病毒具有广泛中和活性的抗体，它们成功克服了这些障碍。在此，我们综述了这些抗体与其病毒抗原在结构特征方面的最新进展，这些进展确定了这些病毒刺突上的一些易受攻击的位点。这些广泛中和抗体往往将其识别重点放在两种病毒之间功能相似的位点上：受体结合位点和膜融合机制。然而，一些识别位点是被中和病毒所特有的，例如HIV - 1 Env上的寡甘露糖碳水化合物的致密屏蔽层。我们在基于结构的设计策略的背景下对这些观察结果进行了讨论，以辅助疫苗设计或抗病毒药物的开发。
Human immunodeficiency virus-1 (HIV-1) envelope protein (Env) and influenza hemagglutinin (HA) are the surface glycoproteins responsible for viral entry into host cells, the first step in the virus life cycle necessary to initiate infection. These glycoproteins exhibit a high degree of sequence variability and glycosylation, which are used as strategies to escape host immune responses. Nonetheless, antibodies with broadly neutralizing activity against these viruses have been isolated that have managed to overcome these barriers. Here, we review recent advances in the structural characterization of these antibodies with their viral antigens that defines a few sites of vulnerability on these viral spikes. These broadly neutralizing antibodies tend to focus their recognition on the sites of similar function between the two viruses: the receptor binding site and membrane fusion machinery. However, some sites of recognition are unique to the virus neutralized, such as the dense shield of oligomannose carbohydrates on HIV-1 Env. These observations are discussed in the context of structure-based design strategies to aid in vaccine design or development of antivirals.
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影响因子：
5.5
作者：
Ahmed FK;Clark BE;Burton DR;Pantophlet R
通讯作者：
Pantophlet R
影响因子：
4.4
作者：
Alfsen, A;Iniguez, P;Bomsel, M
通讯作者：
Bomsel, M
影响因子：
4.8
作者：
Bhattacharyya, Sanchari;Rajan, Roshan Elizabeth;Varadarajan, Raghavan
通讯作者：
Varadarajan, Raghavan
DOI：
10.1126/science.1175868
发表时间：
2009-11-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen L;Kwon YD;Zhou T;Wu X;O'Dell S;Cavacini L;Hessell AJ;Pancera M;Tang M;Xu L;Yang ZY;Zhang MY;Arthos J;Burton DR;Dimitrov DS;Nabel GJ;Posner MR;Sodroski J;Wyatt R;Mascola JR;Kwong PD
通讯作者：
Kwong PD
影响因子：
64.5
作者：
CATON, AJ;BROWNLEE, GG;GERHARD, W
通讯作者：
GERHARD, W