Biology Reference
In-Depth Information
Cytomegalovirus Infection in the Human
Placenta: Maternal Immunity and
Developmentally Regulated Receptors
on Trophoblasts Converge
L. Pereira (
ü
), E. Maidji
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
Spatially Distinct Infection in the Developing Placenta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
Villous Cytotrophoblasts Express EGFR and Upregulate Integrin αV . . . . . . . . . . . . . . . . . . 386
Cell Column Cytotrophoblasts Induce Integrin α1β1 Expression. . . . . . . . . . . . . . . . . . . . . . 388
Replication in Differentiating/Invading Cytotrophoblasts. . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
Infection Impairs Cell Functions Through Diverse Membrane Proximal Events. . . . . . . . . . 391
Implications for Congenital CMV Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
Abstract
During human pregnancy, CMV infects the uterine-placental interface
with varied outcomes from fetal intrauterine growth restriction to permanent birth
defects, depending on the level of maternal immunity and gestational age. Virus
spreads from infected uterine blood vessels, amplifies by replicating in decidual
cells, and disseminates to the placenta in immune complexes. Cytotrophoblasts
- epithelial cells of the placenta - differentiate along two distinct pathways. In the
first, cells fuse into syncytiotrophoblasts covering the surface of chorionic villi that
transport substances from the maternal to fetal bloodstream. In the second, cells
invade the uterine interstitium and blood vessels, remodel the vasculature and form
anchoring villi. CMV initiates replication in cytotrophoblast progenitor cells of
floating villi, whereas syncytiotrophoblasts are spared. This extraordinary pattern
of focal infection in underlying cells hinges on virion receptors being upregulated
as villous cytotrophoblasts begin to differentiate. Expression of developmentally
regulated receptors could explain viral replication in spatially distinct maternal and
fetal compartments. Reduced invasiveness of infected cells could impair remodeling
of the uterine vasculature, restrict maternal blood flow and access of the fetus to
nutrients causing intrauterine growth restriction.
L. Pereira
Department of Cell and Tissue Biology, School of Dentistry, University of California
San Francisco, 513 Parnassus, C-734, Box-0640, San Francisco , 94143 , USA
lenore.pereira@ucsf.edu
