Productive Infection of Bovine Papillomavirus Type 2 in the Placenta of Pregnant Cows Affected with Urinary Bladder Tumors

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.

Bovine papillomavirus: opening new trends for comparative pathology

“…The presence and replication of BPV-2 in the bovine placenta has also been recently demonstrated [5]. Viral particles were demonstrated by electron microscopy in both endometrial and chorionic epithelial cells.…”

“…Research on BPV has led to most of the recent breakthroughs on the biology and pathology of animal papillomavirus, with major implications for human health. Using such spontaneous models, researchers have recently made significant discoveries on the interaction of papillomavirus with chemical carcinogens and immunosuppressants [4], on the role of BPV oncoproteins in cell transformation and immune evasion, on the infection of some unusual cell types and the possibility of haematogenous transplacental BPV transmission [5], as well as on new prophylactic and therapeutic vaccines [6][7][8].…”

Bovine papillomavirus E2 and E5 gene expression in sperm cells of healthy bulls

“…There are few reports focusing on the study of BPV in reproductive tract and its cells [13,35] although the BPV-1 were described in the prepuce and penis [16] and BPV-2 were found infecting placenta and actively expressed in equine semen [30,34]. In an early study, we demonstrate the high incidence of BPV2 in commercial doses of bull semen from national and multinational companies [33].…”

“…In humans, sperm transfected with HPV genes are able to penetrate in oocytes, to deliver HPV genome, and HPV genes can be actively transcribed by the penetrate oocyte [10]. Also, the transplacental transmission of PVs appears to take place in humans and cows [13,27,30].This study adds a new dimension to what we know about BPV transmission mechanisms and pathogenesis. The better understanding of the implications of active BPV-containing semen can contribute to improve strategies to avoid BPV dissemination in the cattle herd and its implications in the reproduction.…”

“…In humans, sperm transfected with HPV genes are able to penetrate in oocytes, to deliver HPV genome, and HPV genes can be actively transcribed by the penetrate oocyte [10]. Also, the transplacental transmission of PVs appears to take place in humans and cows [13,27,30].…”