Monoclonal Antibodies to Different Components of the Human Cytomegalovirus (HCMV) Pentamer gH/gL/pUL128L and Trimer gH/gL/gO as well as Antibodies Elicited during Primary HCMV Infection Prevent Epithelial Cell Syncytium Formation

Détails

ID Serval
serval:BIB_E87CD315D5F9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Monoclonal Antibodies to Different Components of the Human Cytomegalovirus (HCMV) Pentamer gH/gL/pUL128L and Trimer gH/gL/gO as well as Antibodies Elicited during Primary HCMV Infection Prevent Epithelial Cell Syncytium Formation
Périodique
J Virol
Auteur⸱e⸱s
Gerna G., Percivalle E., Perez L., Lanzavecchia A., Lilleri D.
ISSN
0022-538X (Print)
Statut éditorial
Publié
Date de publication
2016
Volume
90
Numéro
14
Pages
6216-6223
Langue
anglais
Notes
1098-5514
Gerna, Giuseppe
Percivalle, Elena
Perez, Laurent
Lanzavecchia, Antonio
Lilleri, Daniele
Journal Article
Research Support, Non-U.S. Gov't
J Virol. 2016 Jun 24;90(14):6216-6223. doi: 10.1128/JVI.00121-16. Print 2016 Jul 15.
Résumé
Human cytomegalovirus (HCMV) may cause disseminated/end-organ disease in congenitally infected newborns and immunosuppressed transplant recipients. Two glycoprotein complexes, gH/gL/gO and gH/gL/pUL128/pUL130/pUL131 (gH/gL/pUL128L; referred to as the pentamer), are required for HCMV entry into fibroblasts and endothelial/epithelial cells, respectively, in the presence of the viral fusion protein gB. In addition, gH/gL/gO was recently reported to also be required for infection of endothelial/epithelial cells. Virus entry into human fibroblasts involves fusion of the virus envelope with the plasma membrane, whereas entry into endothelial/epithelial cells involves macropinocytosis or endocytosis and low-pH-dependent fusion with endosomes. A large set of neutralizing monoclonal antibodies (MAbs), directed to gH, gB, and multiple components of the pentamer, was developed. In addition, novel anti-gO human monoclonal antibodies were recently isolated. It is known that epithelial cell infection with a wild HCMV strain at a high multiplicity of infection produces a large number of syncytia. Incubation of heavily HCMV VR1814-infected ARPE-19 epithelial cells with neutralizing MAbs to one, two, or three components of the pUL128L portion of the pentamer blocked syncytium formation at an antibody concentration of 10 μg/ml, whereas only a partial inhibitory effect was displayed for MAbs to gO, gH, or gB at the same concentration. A blocking effect was also exhibited by convalescent-phase sera from primary HCMV infections. These findings indicate that the pentamer is required for syncytium formation in epithelial cells. IMPORTANCE: Human cytomegalovirus (HCMV) mostly infects epithelial and endothelial cells in vivo Recently, the pentamer protein complex (gH/gL/pUL128L) was identified as being required for infection of these cells, in association with the other protein complex, gH/gL/gO. In primary infections, HCMV migrates to endothelial cells and then to leukocytes, which disseminate the infection throughout the body. The virus then spreads to organs and tissues, mostly infecting either single cells or multinucleated epithelial giant cells (syncytia), depending on the viral load. Potent neutralizing human MAbs directed to distinct binding sites of the pUL128L portion of the pentamer were shown in the past to block virus dissemination. In the present study, MAbs to pUL128L were shown to block syncytium formation with a higher potency than that of MAbs to gO, gH, or gB, thus suggesting their role in limiting virus dissemination. This finding provides additional information useful for the development of anti-HCMV therapeutic antibodies and subunit vaccines.
Mots-clé
Animals, Antibodies, Monoclonal/*immunology, Antibodies, Neutralizing/*immunology, Antibodies, Viral/*immunology, Cells, Cultured, Cytomegalovirus/*immunology, Cytomegalovirus Infections/*immunology/metabolism/virology, Epithelial Cells/immunology/metabolism, Female, Fibroblasts/immunology/metabolism, Giant Cells/*metabolism, Human Umbilical Vein Endothelial Cells/immunology/metabolism, Humans, Membrane Glycoproteins/immunology, Mice, Multiprotein Complexes/immunology, Pregnancy, Viral Envelope Proteins/immunology, Viral Fusion Proteins/*immunology, Virus Internalization
Création de la notice
04/09/2020 20:03
Dernière modification de la notice
07/09/2020 6:26
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