title: Differential expression of the coxsackievirus and adenovirus receptor regulates adenovirus infection of the placenta.
abstract: The molecular mechanisms and pathologic significance of placental viral infections are poorly understood. We investigated factors that regulate placental infection by adenovirus, which is the most common viral pathogen identified in fetal samples from abnormal pregnancies (i.e., fetal growth restriction, oligohydramnios, and nonimmune fetal hydrops). We also determined the pathologic significance of placental adenovirus infection. Northern hybridization, flow cytometry, and immunostaining revealed that placental expression of the coxsackievirus and adenovirus receptor (CAR) varied with gestational age and trophoblast phenotype. The CAR was continuously expressed in invasive or extravillous trophoblast cells but not in villous trophoblast cells. We postulate that the villous syncytiotrophoblast, which does not express CAR and is resistant to adenovirus infection, limits the transplacental transmission of viral pathogens, including adenovirus. Conversely, extravillous trophoblast cells underwent apoptosis when infected by adenovirus in the presence of decidual lymphocytes (which simulated the maternal immune response to viral infection). Thus, adenovirus infection and/or the maternal immune response to adenovirus infection induced the death of placental cell types that expressed CAR. Consequently, we speculate that adenovirus infection of extra-villous trophoblast cells may negatively impact the process of placental invasion and predispose the mother and fetus to adverse reproductive outcomes that result from placental dysfunction.
authors.affiliation: Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: H
authors.initials: H
authors.lastname: Koi
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Makrigiannakis
authors.forename: S
authors.initials: S
authors.lastname: Getsios
authors.forename: C D
authors.initials: CD
authors.lastname: MacCalman
authors.forename: G S
authors.initials: GS
authors.lastname: Kopf
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss
authors.forename: S
authors.initials: S
authors.lastname: Parry
mesh_terms: D000257:Adenoviridae Infections / Q000378:metabolism* / Q000821:virology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001667:Binding, Competitive; D016466:CHO Cells; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D002822:Choriocarcinoma / Q000378:metabolism / Q000821:virology; D006224:Cricetinae; D003656:Decidua / Q000166:cytology / Q000821:virology; D005260:Female; D005865:Gestational Age; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000166:cytology / Q000821:virology; D010922:Placenta Diseases / Q000378:metabolism* / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D011991:Receptors, Virus / Q000096:biosynthesis*; D014327:Trophoblasts / Q000378:metabolism* / Q000821:virology*
chemical_list: D036022:Capsid Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011991:Receptors, Virus; C085301:adenovirus receptor; C105941:coxsackievirus B receptor; C018315:hexon capsid protein, Adenovirus