title: Adeno-associated virus-2 (AAV-2) causes trophoblast dysfunction, and placental AAV-2 infection is associated with preeclampsia.
abstract: 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.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Arechavaleta-Velasco
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Cindy M
authors.initials: CM
authors.lastname: McGrath
authors.forename: Samuel
authors.initials: S
authors.lastname: Parry
mesh_terms: D000257:Adenoviridae Infections / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D000229:Dependovirus / Q000378:metabolism*; D005260:Female; D006801:Humans; D010920:Placenta / Q000821:virology*; D011225:Pre-Eclampsia / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000821:virology*; D014327:Trophoblasts / Q000821:virology*