title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes BHV-1 infection in mammalian cells by interfering with iron homeostasis regulation.
abstract: Mammalian cells require iron to satisfy metabolic needs or to accomplish specialized functions, and DNA viruses, like bovine herpesvirus 1 (BHV-1), require an iron-replete host to efficiently replicate, so that iron bioavailability is an important component of viral virulence. Cellular iron metabolism is coordinately controlled by the Iron Regulatory Proteins (IRP1 and IRP2), whose activity is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a current and persistent environmental contaminant. Considering that TCDD enhances BHV-1 replication, herein we analyzed the effects of TCDD on iron metabolism during BHV-1 infection in MDBK cells, and presented evidences of a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Moreover, an up-regulation of transferrin receptor 1 (TfR1) and a concomitant down-regulation of ferritin were observed. This scenario led to an expansion of the labile iron pool (LIP) and induces a significant enhance of viral titer, as confirmed by increased levels of BHV-1 infected cell protein 0 (bICP0), the major transcriptional regulatory protein of BHV-1. Taken together, our data suggest that TCDD increases the free intracellular iron availability thereby promoting the onset of BHV-1 infection and rendering bovine cells more vulnerable to the virus.
authors.affiliation: Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Fiorito
authors.forename: Carlo
authors.initials: C
authors.lastname: Irace
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Pascale
authors.forename: Alfredo
authors.initials: A
authors.lastname: Colonna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iovane
authors.forename: Ugo
authors.initials: U
authors.lastname: Pagnini
authors.forename: Rita
authors.initials: R
authors.lastname: Santamaria
authors.forename: Luisa
authors.initials: L
authors.lastname: De Martino
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D006566:Herpesviridae Infections / Q000378:metabolism*; D007242:Herpesvirus 1, Bovine / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D035942:Iron Regulatory Protein 2 / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D013723:Teratogens / Q000494:pharmacology*
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2