Abstract
Papillomaviruses (PVs) are believed to be highly epitheliotropic as they usually establish productive infections within stratified epithelia. In vitro, various PVs appear to complete their entire life-cycle in different trophoblastic cell lines. In this study, infection by and protein expression of bovine papillomavirus type 2 (BPV-2) in the uterine and chorionic epithelium of the placenta has been described in four cows suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected both by Western blot analysis and immunohistochemically. It appears to be complexed and perfectly co-localized with the activated platelet-derived growth factor ß receptor (PDGFßR) by laser scanning confocal microscopy. The activated PDGFßR might be involved in organogenesis and neo-angiogenesis rather than in cell transformation during pregnancy. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection has been detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the uterine and chorionic epithelium. Trophoblastic cells appear to be the major target for L1 protein expression. Finally, the early protein E2, required for viral DNA replication and known to be expressed during a productive infection, has been detected by Western blot and immunohistochemically. Electron microscopic investigations detected viral particles in nuclei of uterine and chorionic epithelium. This study shows that both active and productive infections by BPV-2 in the placenta of pregnant cows can occur in vivo.
Highlights
Bovine papillomavirus type 2 (BPV-2) infection is common in cattle on pasture and grazing on bracken fern infested lands
The E5 oncoprotein was detected by immunoprecipitation (Figure 2) and both in the uterine endometrial and chorionic epithelium by immunohistochemistry
human papillomavirus (HPV) DNA has been found in placental trophoblastic cells from women with cervical and/or oral HPV infection history [13] and in trophoblasts of pathological placentas from women with spontaneous abortion [18]
Summary
Bovine papillomavirus type 2 (BPV-2) infection is common in cattle on pasture and grazing on bracken fern infested lands. This often results in tumors of the urinary bladder [1,2]. It is currently presumed that BPV-2 acts synergistically with immunosuppressive, mutagenic and carcinogenic chemicals of bracken fern in molecular pathway(s) leading to bladder carcinogenesis [1]. BPV-1/-2 are closely related serotypes and are the only ones known to infect both epithelial and mesenchymal tissues [5,7]. Similar to other PVs, BPV-1/-2 replication and virion production appear to be confined to the epithelial region of the lesions [7]. New host cell types are emerging [8] and the list of new PV tissue tropisms is still increasing [9,10,11,12]
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