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Unraveling a Three-Step Spatiotemporal Mechanism of Triggering of Receptor-Induced Nipah Virus Fusion and Cell Entry
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نویسنده
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liu q. ,stone j.a. ,bradel-tretheway b. ,dabundo j. ,benavides montano j.a. ,santos-montanez j. ,biering s.b. ,nicola a.v. ,iorio r.m. ,lu x. ,aguilar h.c.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 11
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چکیده
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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. © 2013 liu et al.
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آدرس
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paul g. allen school for global animal health,washington state university,pullman,wa, United States, paul g. allen school for global animal health,washington state university,pullman,wa, United States, paul g. allen school for global animal health,washington state university,pullman,wa, United States, paul g. allen school for global animal health,washington state university,pullman,wa, United States, paul g. allen school for global animal health,washington state university,pullman,wa,united states,departamento ciencia animal,universidad nacional de colombia,palmira valle, Colombia, paul g. allen school for global animal health,washington state university,pullman,wa, United States, paul g. allen school for global animal health,washington state university,pullman,wa, United States, paul g. allen school for global animal health,washington state university,pullman,wa,united states,department of veterinary microbiology and pathology,washington state university,pullman,wa, United States, department of microbiology and physiological systems and program in immunology and microbiology,university of massachusetts medical school,worcester,ma, United States, food,nutrition,and health program,university of british columbia,vancouver,bc, Canada, paul g. allen school for global animal health,washington state university,pullman,wa,united states,department of veterinary microbiology and pathology,washington state university,pullman,wa, United States
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Authors
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