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

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...

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Bibliographic Details
Published in:Viruses 2014-03, Vol.6 (3), p.1346-1364
Main Authors: Zydek, Martin, Petitt, Matthew, Fang-Hoover, June, Adler, Barbara, Kauvar, Lawrence M, Pereira, Lenore, Tabata, Takako
Format: Article
Language:English
Subjects:
Achievement tests
Antibodies, Monoclonal - immunology
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Birth defects
Blood vessels
Cells, Cultured
congenital
Cytomegalovirus
Cytomegalovirus - immunology
Cytomegalovirus - physiology
development
FDA approval
Female
Glycoproteins
HCMV
Human cytomegalovirus
Humans
hyperimmune globulin
Infections
Monoclonal antibodies
neutralization
neutralizing
pentamer
Placenta
Placenta - immunology
Pregnancy
progenitors
Proteins
Stem Cells - virology
trophoblast
Trophoblasts - virology
Viral Envelope Proteins - immunology
Viral Tropism
Virus Internalization
Viruses
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Summary: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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v6031346