title: Epstein-Barr virus permissively infects human syncytiotrophoblasts in vitro and induces replication of human T cell leukemia-lymphoma virus type I in dually infected cells.
abstract: Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1), as well as human T-cell leukemia-lymphoma virus type I (HTLV-I), may interact in the pathogenesis of human retroviral infections. The placental syncytiotrophoblast layer represents a barrier protecting the fetal compartment from exposure to retroviruses. We studied the interactions of EBV with HIV-1 and HTLV-I in human term syncytiotrophoblast cells to investigate the significance of double infections in transplacental transmission of human retroviruses. We found that syncytiotrophoblast cells could be productively infected with EBV. Dual infection of the cells with EBV and HTLV-I resulted in full replication cycle of otherwise latent HTLV-I. In contrast, the restricted permissiveness of syncytiotrophoblasts for HIV-1 was not influenced by coinfection of the cells with EBV. Infection of syncytiotrophoblast cells with EBV, but not HTLV-I, induced interleukin-2 and interleukin-6 secretion, and augmented secretion occurred on coinfection with both viruses. Coinfection of syncytiotrophoblast cells with EBV and HTLV-I induced tumor necrosis factor-beta and transforming growth factor-beta 1 secretion, but infection with either virus alone did not lead to secretion of these cytokines. Permissive replication cycle of HTLV-I was induced by the EBV immediate-early gene product Zta. Pseudotype formation between EBV and HTLV-I in coinfected syncytiotrophoblast cells was not found. Our data suggest that activation of HTLV-I gene expression by EBV in coinfected syncytiotrophoblast cells may be a mechanism for transplacental transmission of HTLV-I.
authors.affiliation: Department of Virus and Cancer, Danish Cancer Society, Aarhus C, Denmark.
authors.forename: F D
authors.initials: FD
authors.lastname: Tóth
authors.forename: G
authors.initials: G
authors.lastname: Aboagye-Mathiesen
authors.forename: J
authors.initials: J
authors.lastname: Nemes
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: I
authors.initials: I
authors.lastname: Andirkó
authors.forename: H
authors.initials: H
authors.lastname: Hager
authors.forename: M
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: J
authors.initials: J
authors.lastname: Szabó
authors.forename: J
authors.initials: J
authors.lastname: Kiss
authors.forename: J
authors.initials: J
authors.lastname: Aranyosi
authors.forename: P
authors.initials: P
authors.lastname: Ebbesen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D016679:Genome, Viral; D015497:HIV-1 / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D011544:Pseudogenes; D015534:Trans-Activators / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000821:virology*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D016207:Cytokines; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins