RT Journal Article SR Electronic(1) A1 Gillet, Laurent A1 Alenquer, Marta A1 Glauser, Daniel L. A1 Colaco, Susanna A1 May, Janet S. A1 Stevenson, Philip G.YR 2009 T1 Glycoprotein L sets the neutralization profile of murid herpesvirus 4 JF Journal of General Virology, VO 90 IS 5 SP 1202 OP 1214 DO https://doi.org/10.1099/vir.0.008755-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.008755-0