title: Wild-type measles virus infection upregulates poliovirus receptor-related 4 and causes apoptosis in brain endothelial cells by induction of tumor necrosis factor-related apoptosis-inducing ligand.
abstract: Small numbers of brain endothelial cells (BECs) are infected in children with neurologic complications of measles virus (MV) infection. This may provide a mechanism for virus entry into the central nervous system, but the mechanisms are unclear. Both in vitro culture systems and animal models are required to elucidate events in the endothelium. We compared the ability of wild-type (WT), vaccine, and rodent-adapted MV strains to infect, replicate, and induce apoptosis in human and murine brain endothelial cells (HBECs and MBECs, respectively). Mice also were infected intracerebrally. All MV stains productively infected HBECs and induced the MV receptor PVRL4. Efficient WT MV production also occurred in MBECs. Extensive monolayer destruction associated with activated caspase 3 staining was observed in HBECs and MBECs, most markedly with WT MV. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), but not Fas ligand, was induced by MV infection. Treatment of MBECs with supernatants from MV-infected MBEC cultures with an anti-TRAIL antibody blocked caspase 3 expression and monolayer destruction. TRAIL was also expressed in the endothelium and other cell types in infected murine brains. This is the first demonstration that infection of low numbers of BECs with WT MV allows efficient virus production, induction of TRAIL, and subsequent widespread apoptosis.
authors.affiliation: From the Centre for Infection and Immunity (HA, CB, SLC), School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, UK; and School of Biological Sciences (BB), Dublin Institute of Technology, Dublin, Ireland.
authors.forename: Hani'ah
authors.initials: H
authors.lastname: Abdullah
authors.forename: Brenda
authors.initials: B
authors.lastname: Brankin
authors.forename: Clare
authors.initials: C
authors.lastname: Brady
authors.forename: Sara Louise
authors.initials: SL
authors.lastname: Cosby
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000821:virology; D006801:Humans; D008457:Measles / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008459:Measles virus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000075983:Nectins
chemical_list: D000906:Antibodies; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; C486698:Nectin4 protein, mouse; D000075983:Nectins