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(American Journal of Pathology. 2006;168:1951-1959.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.050781

Adeno-Associated Virus-2 (AAV-2) Causes Trophoblast Dysfunction, and Placental AAV-2 Infection Is Associated with Preeclampsia

Fabian Arechavaleta-Velasco*, Yujie Ma*, Jian Zhang*, Cindy M. McGrath{dagger} and Samuel Parry*

From the Center for Research on Reproduction and Women’s Health* and the Department of Pathology and Laboratory Medicine,{dagger} University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Shallow invasion by extravillous trophoblast cells into the uterine wall reduces placental perfusion and causes placental dysfunction, but the one or more causes of shallow placental invasion are unknown. We hypothesized that infection with adeno-associated virus-2 (AAV-2) inhibits trophoblast invasion and is associated with preeclampsia, which is a common obstetric complication resulting from placental dysfunction. We determined that transformed extravillous trophoblast (HTR-8/SVneo) cells were susceptible to AAV-2 infection in the presence or absence of adenovirus, which provides helper function for AAV-2 replication, and that AAV-2 infection reduced invasion of HTR-8/SVneo cells through an extracellular matrix before cytopathic effects were detected. In a case-control study, AAV-2 DNA was found more frequently in trophoblast cells from cases of severe preeclampsia (22/40) than from normal term deliveries (5/27, P = 0.002). These results indicate that AAV-2 infection is a previously unidentified cause of placental dysfunction. Additional studies to determine the susceptibility of extravillous trophoblast to other viruses, and the mechanisms by which viral infection impairs placental function, are warranted.




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Copyright © 2006 by the American Society for Investigative Pathology.