title: Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection.
abstract: Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and glycoprotein complexes, which are known to mediate entry into distinct types of host cells. Neutralizing activity was detected in the sera early after primary infection; absorption with a soluble pentameric complex formed by gH/gL/pUL128-131, but not with gH/gL dimer or with gB, abolished the capacity of sera to neutralize infection of epithelial cells. Importantly, an early, high antibody response to pentamer antigenic sites was associated with a significantly reduced risk of HCMV transmission to the fetus. This association is consistent with the high in vitro inhibition of HCMV infection of epithelial/endothelial cells as well as cell-to-cell spreading and virus transfer to leukocytes by anti-pentamer antibodies. Taken together, these findings indicate that the HCMV pentamer complex is a major target of the antibody-mediated maternal immunity.
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione Istituto Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lilleri
authors.forename: Anna
authors.initials: A
authors.lastname: Kabanova
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Revello
authors.forename: Elena
authors.initials: E
authors.lastname: Percivalle
authors.forename: Antonella
authors.initials: A
authors.lastname: Sarasini
authors.forename: Emilia
authors.initials: E
authors.lastname: Genini
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gerna
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D001667:Binding, Competitive; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000635:transmission*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D018445:Infectious Disease Transmission, Vertical; D008562:Membrane Glycoproteins / Q000276:immunology*; D009500:Neutralization Tests; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000821:virology; D011485:Protein Binding; D012044:Regression Analysis; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C077406:UL115 protein, Human herpesvirus 5; C532797:UL128 protein, human cytomegalovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus
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