scholarly journals Bacterial infection of endometrial stromal cells influences bovine herpesvirus 4 immediate early gene activation: a new insight into bacterial and viral interaction for uterine disease

Reproduction ◽  
2008 ◽  
Vol 136 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Gaetano Donofrio ◽  
Lara Ravanetti ◽  
Sandro Cavirani ◽  
Shan Herath ◽  
Antonio Capocefalo ◽  
...  

Experimental infection with the γ-herpesvirus bovine herpesvirus 4 (BoHV-4) rarely establishes disease, yet BoHV-4 is commonly associated with uterine disease in cattle. Uterine disease involves co-infection with bacteria such asEscherichia coli, which stimulate the production of prostaglandin E2(PGE2) by endometrial cells. BoHV-4 replication depends on immediate early 2 (IE2) gene transactivation and, in the present study, PGE2,E. colior its lipopolysaccharide upregulated theIE2gene promoter in uterine cells. Bacterial co-infection is important for BoHV-4 uterine disease.

Reproduction ◽  
2007 ◽  
Vol 134 (1) ◽  
pp. 183-197 ◽  
Author(s):  
Gaetano Donofrio ◽  
Shan Herath ◽  
Chiara Sartori ◽  
Sandro Cavirani ◽  
Cesidio Filippo Flammini ◽  
...  

Bovinepostpartumuterine disease, metritis, affects about 40% of animals and is widely considered to have a bacterial aetiology. Although the γ-herpesvirus bovine herpesvirus 4 (BoHV-4) has been isolated from several outbreaks of metritis or abortion, the role of viruses in endometrial pathology and the mechanisms of viral infection of uterine cells are often ignored. The objectives of the present study were to explore the interaction, tropism and outcomes of BoHV-4 challenge of endometrial stromal and epithelial cells. Endometrial stromal and epithelial cells were purified and infected with a recombinant BoHV-4 carrying an enhanced green fluorescent protein (EGFP) expression cassette to monitor the establishment of infection. BoHV-4 efficiently infected both stromal and epithelial cells, causing a strong non-apoptotic cytopathic effect, associated with robust viral replication. The crucial step for the BoHV-4 endometriotropism appeared to be after viral entry as there was enhanced transactivation of the BoHV-4 immediate early 2 gene promoter following transient transfection into the endometrial cells. Infection with BoHV-4 increased cyclooxygenase 2 protein expression and prostaglandin estradiol secretion in endometrial stromal cells, but not epithelial cells. Bovine macrophages are persistently infected with BoHV-4, and co-culture with endometrial stromal cells reactivated BoHV-4 replication in the persistently infected macrophages, suggesting a symbiotic relationship between the cells and virus. In conclusion, the present study provides evidence of cellular and molecular mechanisms, supporting the concept that BoHV-4 is a pathogen associated with uterine disease.


2011 ◽  
Vol 148 (2-4) ◽  
pp. 219-231 ◽  
Author(s):  
Valentina Franceschi ◽  
Antonio Capocefalo ◽  
Lara Ravanetti ◽  
Alain Vanderplasschen ◽  
Laurent Gillet ◽  
...  

2004 ◽  
Vol 85 (2) ◽  
pp. 355-367 ◽  
Author(s):  
Nicolas Markine-Goriaynoff ◽  
Laurent Gillet ◽  
Odd A. Karlsen ◽  
Lars Haarr ◽  
Frédéric Minner ◽  
...  

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only virus gene known to date that encodes a homologue of the cellular core 2 β-1,6-N-acetylglucosaminyltransferase-mucine type (C2GnT-M). Recently, our phylogenetic study revealed that the Bo17 gene has been acquired from an ancestor of the African buffalo around 1·5 million years ago. Despite this recent origin, the Bo17 sequence has spread to fixation in the virus population possibly by natural selection. Supporting the latter hypothesis, it has been shown by our group for the V. test strain that Bo17 is expressed during BoHV-4 replication in vitro, and that Bo17 expression product (pBo17) has all three enzymic activities exhibited by cellular C2GnT-M, i.e. core 2, core 4 and I branching activities. In the present study, firstly it was investigated whether encoding a functional C2GnT-M is a general property of BoHV-4 strains. Analysis of nine representative strains of the BoHV-4 species revealed that all of them express the Bo17 gene and the associated core 2 branching activity during virus replication in vitro. Secondly, in order to investigate the roles of Bo17, its kinetic class of expression was analysed and a deleted recombinant strain was produced. These experiments revealed that Bo17 is expressed as an early gene which is not essential for virus replication in vitro. However, comparison of the structural proteins, produced by the wild-type, the revertant and the deleted viruses, by 2D gels demonstrated that pBo17 contributes to the post-translational modifications of structural proteins. Possible roles of Bo17 in vivo are discussed.


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