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 ComplexReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA

2

Division of Virology, Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, Pettenkoferstr. 9A, D-80336 Munich, Germany

3

Trellis Bioscience, LLC, 2-B Corporate Drive, South San Francisco, CA 94080, USA





*

Author to whom correspondence should be addressed.



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. View Full-Text

Keywords: HCMV; congenital; trophoblast; progenitors; neutralizing; placenta; development; neutralization; pentamer; hyperimmune globulin HCMV; congenital; trophoblast; progenitors; neutralizing; placenta; development; neutralization; pentamer; hyperimmune globulin





Autor: Martin Zydek 1, Matthew Petitt 1, June Fang-Hoover 1, Barbara Adler 2, Lawrence M. Kauvar 3, Lenore Pereira 1,* and Takako Tabata 1

Fuente: http://mdpi.com/



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