RT Journal Article SR Electronic(1) A1 Glauser, Daniel L. A1 Gillet, Laurent A1 Stevenson, Philip G.YR 2012 T1 Virion endocytosis is a major target for murid herpesvirus-4 neutralization JF Journal of General Virology, VO 93 IS 6 SP 1316 OP 1327 DO https://doi.org/10.1099/vir.0.040790-0 PB Microbiology Society, SN 1465-2099, AB Herpesviruses consistently transmit from immunocompetent carriers, implying that their neutralization is hard to achieve. Murid herpesvirus-4 (MuHV-4) exploits host IgG Fc receptors to bypass blocks to cell binding, and pH-dependent protein conformation changes to unveil its fusion machinery only after endocytosis. Nevertheless, neutralization remains possible by targeting the virion glycoprotein H (gH)–gL heterodimer, and the neutralizing antibody responses of MuHV-4 carriers are improved by boosting with recombinant gH–gL. We analysed here how gH–gL-directed neutralization works. The MuHV-4 gH–gL binds to heparan sulfate. However, most gH–gL-specific neutralizing antibodies did not block this interaction; neither did they act directly on fusion. Instead, they blocked virion endocytosis and transport to the late endosomes, where membrane fusion normally occurs. The poor endocytosis of gH–gL-neutralized virions was recapitulated precisely by virions genetically lacking gL. Therefore, driving virion uptake appears to be an important function of gH–gL that provides a major target for antibody-mediated neutralization., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.040790-0