%0 Journal Article %A Gillet, Laurent %A Alenquer, Marta %A Glauser, Daniel L. %A Colaco, Susanna %A May, Janet S. %A Stevenson, Philip G. %T Glycoprotein L sets the neutralization profile of murid herpesvirus 4 %D 2009 %J Journal of General Virology, %V 90 %N 5 %P 1202-1214 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.008755-0 %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.008755-0