Viruses 2014, 6(3), 1346-1364; doi:10.3390/v6031346
Article

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

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Received: 22 January 2014; in revised form: 27 February 2014 / Accepted: 27 February 2014 / Published: 19 March 2014
(This article belongs to the Special Issue Recent CMV Research)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: HCMV; congenital; trophoblast; progenitors; neutralizing; placenta; development; neutralization; pentamer; hyperimmune globulin
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MDPI and ACS Style

Zydek, M.; Petitt, M.; Fang-Hoover, J.; Adler, B.; Kauvar, L.M.; Pereira, L.; Tabata, T. 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. Viruses 2014, 6, 1346-1364.

AMA Style

Zydek M, Petitt M, Fang-Hoover J, Adler B, Kauvar LM, Pereira L, Tabata T. 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. Viruses. 2014; 6(3):1346-1364.

Chicago/Turabian Style

Zydek, Martin; Petitt, Matthew; Fang-Hoover, June; Adler, Barbara; Kauvar, Lawrence M.; Pereira, Lenore; Tabata, Takako. 2014. "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." Viruses 6, no. 3: 1346-1364.

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