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Journal of Virology, August 2000, p. 6808-6820, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Cytomegalovirus Infection of Placental Cytotrophoblasts In Vitro and In Utero: Implications for Transmission and Pathogenesis

Susan Fisher,1,2,3,4,5,* Olga Genbacev,1 Ekaterina Maidji,1 and Lenore Pereira1,*

Departments of Stomatology,1 Obstetrics, Gynecology and Reproductive Sciences,2 Anatomy,3 and Pharmaceutical Chemistry4 and the Biomedical Sciences Graduate Program,5 University of California San Francisco, San Francisco, California 94143

Received 8 March 2000/Accepted 28 April 2000

Human cytomegalovirus (CMV) 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 CMV 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.

* Corresponding author. Mailing address: Department of Stomatology, HSW-604, University of California San Francisco, 513 Parnassus Ave., San Francisco, CA 94143-0512. Phone: (415) 476-5297 (S.F.), (415) 476-8248 (L.P.). Fax: (415) 502-7338. E-mail: sfisher{at}cgl.ucsf.edu or pereira{at}itsa.ucsf.edu.

Journal of Virology, August 2000, p. 6808-6820, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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