Journal article
Unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced Nipah virus fusion and cell entry
PLoS pathogens, Vol.9(11), pp.e1003770-e1003770
2013
Handle:
https://hdl.handle.net/2376/115158
PMCID: PMC3837712
PMID: 24278018
Abstract
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.
Metrics
4 Record Views
Details
- Title
- Unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced Nipah virus fusion and cell entry
- Creators
- Qian Liu - Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of AmericaJacquelyn A StoneBirgit Bradel-TrethewayJeffrey DabundoJavier A Benavides MontanoJennifer Santos-MontanezScott B BieringAnthony V NicolaRonald M IorioXiaonan LuHector C Aguilar
- Publication Details
- PLoS pathogens, Vol.9(11), pp.e1003770-e1003770
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
- Publisher
- United States
- Grant note
- NIH AI094329 / NIAID NIH HHS T32 GM008336 / NIGMS NIH HHS NIH T32GM008336 / NIGMS NIH HHS R21 AI094329 / NIAID NIH HHS
- Identifiers
- 99900547872301842
- Language
- English
- Resource Type
- Journal article