title: Bovine endometrial stromal cells support tumor necrosis factor alpha-induced bovine herpesvirus type 4 enhanced replication.
abstract: Bovine uterine infections are the most important cause of economic losses in the cattle industry. Although the etiology of uterine diseases is mainly ascribed to bacterial infection, they can also be associated with viral infection, such as bovine herpesvirus 4 (BoHV-4), which is often a secondary agent following bacteria. Besides microbial infection, many inflammatory molecules belonging to the innate immune response orchestrate the outcome of the infection. In the present study, the interaction between BoHV-4-infected bovine endometrial stromal cells and tumor necrosis factor alpha (TNF-alpha) was investigated. Bovine herpesvirus 4 possesses a special tropism toward endometrial stromal cells. For this reason, a simian virus 40 (SV40) immortalized endometrial stromal cell line (SV40BESC) was established; it was proven that it was stable, it expressed toll-like receptors (TLRs; from 1 to 10) and TNF-alpha receptors I and II, and it was responsive to exogenous TNF-alpha. Further, an increase of BoHV-4 replication and cytopathic effect was observed in BoHV-4-infected and TNF-alpha-treated SV40BESCs. This increase of viral replication was associated with BoHV-4 immediate early 2 (IE2) gene promoter trans-activation through the interaction of the nuclear factor KB (NFKB) with the putative NFKB-responsive elements found within BoHV-4 IE2 gene promoter, and this interaction was abolished when NFKB-responsive elements were deleted. These data shed light on two important and rather controversial issues: the role of TNF-alpha receptor, which is weakly expressed in the stromal layer of the bovine uterus, as well as the possible interactions between proinflammatory molecules, viral replication, and chronic uterine disease.
authors.affiliation: Department of Medical-Veterinary Science, University of Parma, Parma, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jacca
authors.forename: Valentina
authors.initials: V
authors.lastname: Franceschi
authors.forename: Angelo
authors.initials: A
authors.lastname: Colagiorgi
authors.forename: Martin
authors.initials: M
authors.lastname: Sheldon
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D026021:Herpesvirus 4, Bovine / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: C079185:IE2 protein, bovine herpesvirus type 4; D017874:Immediate-Early Proteins; D018124:Receptors, Tumor Necrosis Factor; D051193:Toll-Like Receptors; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha
keywords: bovine endometrial stromal cells; bovine herpesvirus 4; chemokine; interleukin 8; postpartum metritis