Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: Implications for transmission and pathogenesis

被引:262
作者
Fisher, S
Genbacev, O
Maidji, E
Pereira, L
机构
[1] Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA
关键词
D O I
10.1128/JVI.74.15.6808-6820.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human cytomegalovirus (CR;TV) is the leading cause of prenatal viral infection, Affected infants may suffer intrauterine growth retardation and serious neurologic impairment. Analysis of spontaneously aborted conceptuses shows that CMV infects the placenta before the embryo or fetus. In the human hemochorial placenta, maternal blood directly contacts syncytiotrophoblasts that cover chorionic villi and cytotrophoblasts that invade uterine vessels, suggesting possible routes for CMV transmission. To test this hypothesis, we exposed first-trimester chorionic villi and isolated cytotrophoblasts to CMV in vitro. In chorionic villi, syncytiotrophoblasts did not become infected, although clusters of underlying cytotrophoblasts expressed viral proteins. In chorionic villi that were infected with CR IV in utero, syncytiotrophoblasts were often spared whereas cytotrophoblasts and other cells of the villous core expressed viral proteins, Isolated cytotrophoblasts were also permissive for CMV replication in vitro; significantly, infection subsequently impaired the cytotrophoblasts' ability to differentiate and invade, These results suggest two possible routes of CMV transmission to the fetus: (i) across syncytiotrophoblasts with subsequent infection of the underlying cytotrophoblasts and (ii) via invasive cytotrophoblasts within the uterine wall. Furthermore, the observation that CMV infection impairs critical aspects of cytotrophoblast function offers testable hypotheses for explaining the deleterious effects of this virus on pregnancy outcome.
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页码:6808 / 6820
页数:13
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