title: Apoptotic activity in villous trophoblast cells during B19 infection correlates with clinical outcome: assessment by the caspase-related M30 Cytodeath antibody.
abstract: Human parvovirus B19 (B19) infection during pregnancy can result in horizontal transmission of the virus and congenital infection. The main targets for B19 replication are the erythroid precursor cell of the colony and burst forming units. The cellular receptor necessary for B19 infectivity is globoside. Other non-erythroid cells can express this receptor, including megakaryocytes, endothelial cells, cardiac myocytes and placental trophoblast cells. B19 infection of globoside-containing erythroid cells results in cell death via apoptosis. We asked whether globoside-containing placental trophoblast cells, although not permissive for complete viral replication, would show evidence of apoptotic activity as a result of B19 infection. Placentas from 26 pregnancies with documented maternal and/or congenital B19 infection, 14 with poor outcomes and 12 with good outcomes were examined for evidence of apoptosis using the caspase-related M30 Cytodeath monoclonal antibody (Mab). M30 Mab recognizes a caspase 3 directed cleavage event within cytokeratin 18, a protein widely distributed in epithelial cells, of which trophoblast cells are classified. The results of the immunohistochemical analysis revealed a significant number of M30-staining placental villous trophoblast cells from B19-complicated pregnancies with poor outcomes compared to B19-complicated pregnancies with good outcomes or the 24 age-matched controls (P< 0.001). This is the first description of an association between B19-complicated pregnancies ending in foetal death and increased apoptosis within placental villous trophoblast cells. Damage due to premature death of the protective barrier of the placental trophoblast layer may compromise its integrity and play a role in pathogenesis.
authors.affiliation: University of Pittsburgh, Department of Pathology, 204 Craft Avenue, Pittsburgh, PA 15213, USA. jordanja@pitt.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Jordan
authors.forename: A R
authors.initials: AR
authors.lastname: Butchko
mesh_terms: D000911:Antibodies, Monoclonal; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007633:Keratins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D010322:Parvoviridae Infections / Q000473:pathology*; D016732:Parvovirus B19, Human / Q000235:genetics; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology / Q000821:virology*; D011256:Pregnancy Outcome; D012189:Retrospective Studies; D014327:Trophoblasts / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D007633:Keratins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases