期刊论文详细信息
PLoS Pathogens
Unraveling a Three-Step Spatiotemporal Mechanism of Triggering of Receptor-Induced Nipah Virus Fusion and Cell Entry
Jennifer Santos-Montanez1  Hector C. Aguilar2  Xiaonan Lu3  Javier A. Benavides Montano4  Jeffrey Dabundo4  Anthony V. Nicola4  Jacquelyn A. Stone4  Scott B. Biering4  Qian Liu4  Ronald M. Iorio4  Birgit Bradel-Tretheway4 
[1] Departamento Ciencia Animal, Universidad Nacional de Colombia, Palmira Valle, Colombia;Department of Microbiology and Physiological Systems and Program in Immunology and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America;Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America;Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America
关键词: Membrane fusion;    Virions;    Cell fusion;    Cell binding;    Viral entry;    Flow cytometry;    Paramyxoviruses;    293T cells;   
DOI  :  10.1371/journal.ppat.1003770
学科分类:生物科学(综合)
来源: Public Library of Science
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【 摘 要 】

Membrane fusion is essential for entry of the biomedically-important paramyxoviruses into their host cells (viral-cell fusion), and for syncytia formation (cell-cell fusion), often induced by paramyxoviral infections [e.g. those of the deadly Nipah virus (NiV)]. For most paramyxoviruses, membrane fusion requires two viral glycoproteins. Upon receptor binding, the attachment glycoprotein (HN/H/G) triggers the fusion glycoprotein (F) to undergo conformational changes that merge viral and/or cell membranes. However, a significant knowledge gap remains on how HN/H/G couples cell receptor binding to F-triggering. Via interdisciplinary approaches we report the first comprehensive mechanism of NiV membrane fusion triggering, involving three spatiotemporally sequential cell receptor-induced conformational steps in NiV-G: two in the head and one in the stalk. Interestingly, a headless NiV-G mutant was able to trigger NiV-F, and the two head conformational steps were required for the exposure of the stalk domain. Moreover, the headless NiV-G prematurely triggered NiV-F on virions, indicating that the NiV-G head prevents premature triggering of NiV-F on virions by concealing a F-triggering stalk domain until the correct time and place: receptor-binding. Based on these and recent paramyxovirus findings, we present a comprehensive and fundamentally conserved mechanistic model of paramyxovirus membrane fusion triggering and cell entry.

【 授权许可】

CC BY   

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