Reference : Glycoprotein L sets the neutralization profile of murid herpesvirus 4.
Scientific journals : Article
Life sciences : Microbiology
http://hdl.handle.net/2268/75671
Glycoprotein L sets the neutralization profile of murid herpesvirus 4.
English
Gillet, Laurent mailto [Université de Liège - ULg > > Immunologie et vaccinologie >]
Alenquer, Marta [> > > >]
Glauser, Daniel L [> > > >]
Colaco, Susanna [> > > >]
May, Janet S [> > > >]
Stevenson, Philip G [> > > >]
2009
Journal of General Virology (The)
Society for General Microbiology
90
Pt 5
1202-14
Yes (verified by ORBi)
International
0022-1317
1465-2099
London
United Kingdom
[en] Animals ; Antibodies, Viral/immunology ; CHO Cells ; Cell Line ; Cricetinae ; Cricetulus ; Epithelial Cells ; Female ; Fibroblasts ; Glycoproteins/immunology ; Macrophages ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Protein Binding ; Rhadinovirus/immunology/metabolism ; Viral Envelope Proteins/immunology
[en] Antibodies readily neutralize acute, epidemic viruses, but are less effective against more indolent pathogens such as herpesviruses. Murid herpesvirus 4 (MuHV-4) provides an accessible model for tracking the fate of antibody-exposed gammaherpesvirus virions. Glycoprotein L (gL) plays a central role in MuHV-4 entry: it allows gH to bind heparan sulfate and regulates fusion-associated conformation changes in gH and gB. However, gL is non-essential: heparan sulfate binding can also occur via gp70, and the gB-gH complex alone seems to be sufficient for membrane fusion. Here, we investigated how gL affects the susceptibility of MuHV-4 to neutralization. Immune sera neutralized gL(-) virions more readily than gL(+) virions, chiefly because heparan sulfate binding now depended on gp70 and was therefore easier to block. However, there were also post-binding effects. First, the downstream, gL-independent conformation of gH became a neutralization target; gL normally prevents this by holding gH in an antigenically distinct heterodimer until after endocytosis. Second, gL(-) virions were more vulnerable to gB-directed neutralization. This covered multiple epitopes and thus seemed to reflect a general opening up of the gH-gB entry complex, which gL again normally restricts to late endosomes. gL therefore limits MuHV-4 neutralization by providing redundancy in cell binding and by keeping key elements of the virion fusion machinery hidden until after endocytosis.
http://hdl.handle.net/2268/75671
10.1099/vir.0.008755-0

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