title: HCMV infection of human trophoblast progenitor cells of the placenta is neutralized by a human monoclonal antibody to glycoprotein B and not by antibodies to the pentamer complex.
abstract: Human cytomegalovirus (HCMV) is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs), the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs) give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs). Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A) showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb), TRL345, reactive with glycoprotein B (gB), but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease.
authors.affiliation: Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. martin.zydek@ucsf.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Zydek
authors.affiliation: Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. matthew.petitt@ucsf.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Petitt
authors.affiliation: Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. june.fang-hoover@ucsf.edu.
authors.forename: June
authors.initials: J
authors.lastname: Fang-Hoover
authors.affiliation: Division of Virology, Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, Pettenkoferstr. 9A, D-80336 Munich, Germany. adler_b@mvp.uni-muenchen.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Adler
authors.affiliation: Trellis Bioscience, LLC, 2-B Corporate Drive, South San Francisco, CA 94080, USA. lkauvar@trellisbio.com.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Kauvar
authors.affiliation: Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. lenore.pereira@ucsf.edu.
authors.forename: Lenore
authors.initials: L
authors.lastname: Pereira
authors.affiliation: Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. takako.tabata@ucsf.edu.
authors.forename: Takako
authors.initials: T
authors.lastname: Tabata
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D005260:Female; D006801:Humans; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D013234:Stem Cells / Q000821:virology*; D014327:Trophoblasts / Q000821:virology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D056189:Viral Tropism; D053586:Virus Internalization
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus