Membrane interactions of the tick-borne encephalitis virus fusion protein E at low pH

Journal of Virology
Karin StiasnyF X Heinz

Abstract

Membrane fusion of the flavivirus tick-borne encephalitis virus is triggered by the mildly acidic pH of the endosome and is mediated by envelope protein E, a class II viral fusion protein. The low-pH trigger induces an oligomeric rearrangement in which the subunits of the native E homodimers dissociate and the monomeric subunits then reassociate into homotrimers. Here we provide evidence that membrane binding is mediated by the intermediate monomeric form of E, generated by low-pH-induced dissociation of the dimer. Liposome coflotation experiments revealed that association with target membranes occurred only when liposomes were present at the time of acidification, whereas pretreating virions at low pH in the absence of membranes resulted in the loss of their ability to stably attach to liposomes. With the cleavable cross-linker ethylene glycolbis(succinimidylsuccinate), it was shown that a truncated soluble form of the E protein (sE) could bind to membranes only when the dimers were free to dissociate at low pH, and binding could be blocked by a monoclonal antibody that recognizes the fusion peptide, which is at the distal tip of the E monomer but is buried in the native dimer. Surprisingly, analysis of the membrane-associated...Continue Reading

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Citations

May 13, 2008·Expert Reviews in Molecular Medicine·Theodore C Pierson, Michael S Diamond
Dec 21, 2004·Nature Reviews. Microbiology·Suchetana MukhopadhyayMichael G Rossmann
Dec 17, 2005·Nature Reviews. Microbiology·Margaret Kielian, Félix A Rey
Jul 4, 2008·Nature Structural & Molecular Biology·Stephen C Harrison
Sep 16, 2006·Journal of Virology·Karin StiasnyFranz X Heinz
Aug 3, 2007·Journal of Virology·Karin StiasnyFranz X Heinz
Dec 17, 2009·Journal of Virology·Shane D TraskPhilip R Dormitzer
Nov 2, 2012·Journal of Virology·Vincent C LucaDaved H Fremont
Jun 24, 2011·Journal of Virology·Karen PangerlKarin Stiasny
Jun 28, 2003·Journal of Virology·Karin StiasnyFranz X Heinz
Mar 16, 2004·Journal of Virology·Don L GibbonsMargaret Kielian
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Jan 28, 2006·Journal of Virology·Donna M TscherneCharles M Rice
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Jun 12, 2012·Vaccine·Franz X Heinz, Karin Stiasny

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