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Glycoprotein L sets the neutralization profile of murid herpesvirus 4

Laurent Gillet

Marta Alenquer

Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK

Correspondence
Philip G. Stevenson
pgs27{at}cam.ac.uk

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.

Present address: Immunology–Vaccinology, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.

Present address: Instituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

This article has been cited by other articles:

				D. E. Wright, S. Colaco, C. Colaco, and P. G. Stevenson Antibody limits in vivo murid herpesvirus-4 replication by IgG Fc receptor-dependent functions J. Gen. Virol., November 1, 2009; 90(11): 2592 - 2603. [Abstract] [Full Text] [PDF]

				P. G. Stevenson, J. P. Simas, and S. Efstathiou Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4 J. Gen. Virol., October 1, 2009; 90(10): 2317 - 2330. [Abstract] [Full Text] [PDF]