Virion endocytosis is a major target for Murid Herpesvirus-4 neutralization

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 af...

Full description

Saved in:
Bibliographic Details
Published in:Journal of general virology 2012-06, Vol.93 (Pt 6), p.1316-1327
Main Authors: Glauser, D, Gillet, Laurent, Stevenson, PG
Format: Article
Language:English
Subjects:
Animal
Animals
Antibodies, Neutralizing - immunology
Biological and medical sciences
Cell Line
Cricetinae
Endocytosis
Fundamental and applied biological sciences. Psychology
Herpesviridae Infections - immunology
Herpesviridae Infections - physiopathology
Herpesviridae Infections - veterinary
Herpesviridae Infections - virology
Life sciences
Mice
Microbiologie
Microbiology
Miscellaneous
Neutralization Tests
Rhadinovirus - genetics
Rhadinovirus - immunology
Rhadinovirus - physiology
Rodent Diseases - immunology
Rodent Diseases - physiopathology
Rodent Diseases - virology
Sciences du vivant
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Virion - genetics
Virion - immunology
Virion - physiology
Virology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1317
1465-2099
1465-2099
DOI:10.1099/vir.0.040790-0