Cytomegalovirus Impairs Cytotrophoblast-Induced Lymphangiogenesis and Vascular Remodeling in an in Vivo Human Placentation Model
Identifieur interne : 004398 ( Main/Exploration ); précédent : 004397; suivant : 004399Cytomegalovirus Impairs Cytotrophoblast-Induced Lymphangiogenesis and Vascular Remodeling in an in Vivo Human Placentation Model
Auteurs : Takako Tabata [États-Unis] ; Matthew Petitt [États-Unis] ; June Fang-Hoover [États-Unis] ; Jose Rivera [États-Unis] ; Naoki Nozawa [Japon] ; Stephen Shiboski [États-Unis] ; Naoki Inoue [Japon] ; Lenore Pereira [États-Unis]Source :
- The American Journal of Pathology [ 0002-9440 ] ; 2012.
Abstract
We investigated human cytomegalovirus pathogenesis by comparing infection with the low-passage, endotheliotropic strain VR1814 and the attenuated laboratory strain AD169 in human placental villi as explants
Url:
DOI: 10.1016/j.ajpath.2012.08.003
PubMed: 22959908
PubMed Central: 3483806
Affiliations:
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<author><name sortKey="Tabata, Takako" sort="Tabata, Takako" uniqKey="Tabata T" first="Takako" last="Tabata">Takako Tabata</name>
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<author><name sortKey="Fang Hoover, June" sort="Fang Hoover, June" uniqKey="Fang Hoover J" first="June" last="Fang-Hoover">June Fang-Hoover</name>
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<series><title level="j">The American Journal of Pathology</title>
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<front><div type="abstract" xml:lang="en"><p>We investigated human cytomegalovirus pathogenesis by comparing infection with the low-passage, endotheliotropic strain VR1814 and the attenuated laboratory strain AD169 in human placental villi as explants <italic>in vitro</italic>
and xenografts transplanted into kidney capsules of SCID mice (ie, mice with severe combined immunodeficiency). In this <italic>in vivo</italic>
human placentation model, human cytotrophoblasts invade the renal parenchyma, remodel resident arteries, and induce a robust lymphangiogenic response. VR1814 replicated in villous and cell column cytotrophoblasts and reduced formation of anchoring villi <italic>in vitro</italic>
. In xenografts, infected cytotrophoblasts had a severely diminished capacity to invade and remodel resident arteries. Infiltrating lymphatic endothelial cells proliferated, aggregated, and failed to form lymphatic vessels. In contrast, AD169 grew poorly in cytotrophoblasts in explants, and anchoring villi formed normally <italic>in vitro</italic>
. Likewise, viral replication was impaired in xenografts, and cytotrophoblasts retained invasive capacity, but some partially remodeled blood vessels incorporated lymphatic endothelial cells and were permeable to blood. The expression of both vascular endothelial growth factor (VEGF)-C and basic fibroblast growth factor increased in VR1814-infected explants, whereas VEGF-A and soluble VEGF receptor-3 increased in those infected with AD169. Our results suggest that viral replication and paracrine factors could undermine vascular remodeling and cytotrophoblast-induced lymphangiogenesis, contributing to bleeding, hypoxia, and edema in pregnancies complicated by congenital human cytomegalovirus infection.</p>
</div>
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<name sortKey="Fang Hoover, June" sort="Fang Hoover, June" uniqKey="Fang Hoover J" first="June" last="Fang-Hoover">June Fang-Hoover</name>
<name sortKey="Pereira, Lenore" sort="Pereira, Lenore" uniqKey="Pereira L" first="Lenore" last="Pereira">Lenore Pereira</name>
<name sortKey="Petitt, Matthew" sort="Petitt, Matthew" uniqKey="Petitt M" first="Matthew" last="Petitt">Matthew Petitt</name>
<name sortKey="Rivera, Jose" sort="Rivera, Jose" uniqKey="Rivera J" first="Jose" last="Rivera">Jose Rivera</name>
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<country name="Japon"><region name="Région de Kantō"><name sortKey="Nozawa, Naoki" sort="Nozawa, Naoki" uniqKey="Nozawa N" first="Naoki" last="Nozawa">Naoki Nozawa</name>
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<name sortKey="Inoue, Naoki" sort="Inoue, Naoki" uniqKey="Inoue N" first="Naoki" last="Inoue">Naoki Inoue</name>
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