Glycoprotein L sets the neutralization profile of murid herpesvirus 4

Gillet, Laurent, Alenquer, Marta, Glauser, Daniel L., Colaco, Susanna, May, Janet S. and Stevenson, Philip G. (2009) Glycoprotein L sets the neutralization profile of murid herpesvirus 4. Journal of General Virology, 90 5: 1202-1214. doi:10.1099/vir.0.008755-0


Author Gillet, Laurent
Alenquer, Marta
Glauser, Daniel L.
Colaco, Susanna
May, Janet S.
Stevenson, Philip G.
Title Glycoprotein L sets the neutralization profile of murid herpesvirus 4
Journal name Journal of General Virology   Check publisher's open access policy
ISSN 0022-1317
1465-2099
Publication date 2009
Year available 2009
Sub-type Article (original research)
DOI 10.1099/vir.0.008755-0
Open Access Status
Volume 90
Issue 5
Start page 1202
End page 1214
Total pages 13
Place of publication Reading, Berks, United Kingdom
Publisher Society for General Microbiology
Collection year 2010
Language eng
Subject 2406 Virology
Abstract 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Clinical Medical Virology Centre Publications
 
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