The molecular basis of HIV entry.

The molecular basis of HIV entry.
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DOI:
10.1111/j.1462-5822.2012.01812.x
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发表时间:
2012-08
影响因子:
3.4
通讯作者:
Klasse PJ
Klasse PJ
中科院分区:
生物学2区
文献类型:
--
作者:
Klasse PJ

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当病毒附着在易感细胞上时,HIV 感染就开始了。为了让病毒继续复制,病毒包膜必须与细胞膜融合,从而将病毒核心传递到细胞质,RNA 基因组在细胞质中进行逆转录。通过融合进入这一过程的关键参与者是病毒侧的包膜糖蛋白,以及细胞侧的 CD4 和辅助受体 CCR5 或 CXCR4。在这里,从细胞生物学、结构、机制和基于建模的角度回顾了这些分子的相互作用。评估有关进入细胞区室、病毒通过细胞与细胞直接接触的转移、分子事件的顺序以及病毒-细胞分裂两侧涉及的分子数量的假设。一个新兴的主题是两侧进入介体之间的异质性,这种多样性影响进入抑制剂的功效,无论是小分子配体、肽还是中和抗体。这些见解为合理的治疗和疫苗接种策略提供了信息。
Infection by HIV starts when the virus attaches to a susceptible cell. For viral replication to continue, the viral envelope must fuse with a cellular membrane, thereby delivering the viral core to the cytoplasm, where the RNA genome is reverse‐transcribed. The key players in this entry by fusion are the envelope glycoprotein, on the viral side, and CD4 and a co‐receptor, CCR5 or CXCR4, on the cellular side. Here, the interplay of these molecules is reviewed from cell‐biological, structural, mechanistic, and modelling‐based perspectives. Hypotheses are evaluated regarding the cellular compartment for entry, the transfer of virus through direct cell‐to‐cell contact, the sequence of molecular events, and the number of molecules involved on each side of the virus–cell divide. An emerging theme is the heterogeneity among the entry mediators on both sides, a diversity that affects the efficacy of entry inhibitors, be they small‐molecule ligands, peptides or neutralizing antibodies. These insights inform rational strategies for therapy as well as vaccination.
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