Oral fibropapillomatosis and epidermal hyperplasia of the lip in newborn lambs associated with bovine Deltapapillomavirus

Abstract

Congenital fibropapillomatosis of the gingiva and oral mucosa and epidermal hyperplasia of the lip are described, for the first time, in two newborn lambs. Expression of the E5 oncoprotein of bovine deltapapillomavirus types 2 (BPV-2) and -13 (BPV-13) was detected in both fibropapillomas and the hyperplastic epidermal cells suggesting the BPV infection was the cause of the proliferative lesions. No DNA sequences of BPV-1 and BPV-14 were detected. Both BPV-2 and BPV-13 DNA were also amplified from peripheral blood mononuclear cells (PBMCs) of the newborn lambs’ dams. The concordance between BPV genotypes detected in the blood of dam and the oral and skin pathological samples of their offspring suggests that a vertical hematogeneous transmission was most likely source of BPV infection. Immunoblotting revealed the presence of E5 dimers allowing the viral protein to be biologically active. E5 dimers bind and activate the platelet derived growth factor β receptor (PDGFβR), a major molecular mechanism contributing to disease. The detection of E5 protein within the proliferating cells therefore adds further evidence that the BPV infection was the cause of the proliferative lesions seen in these lambs. This is the first evidence of vertical transmission of BPVs in sheep resulting in a clinical disease.

Bovine Papillomavirus Type 2 Infection Associated with Papillomatosis of the Amniotic Membrane in Water Buffaloes (Bubalus bubalis)

“…Although the initial development and progression of the papillomas was not investigated, it is possible that foci of squamous epithelial cells harbor BPV DNA and are natural cell sites that may allow the life cycle of BPVs. Infection of the placenta by BPVs has been shown in cattle [41] and transplacental BPV infection has been suggested for several species including sheep [10], cattle [32], and horses [42]. Therefore, it is possible that the foci of squamous metaplasia may allow infection by the BPVs and in the presently described buffaloes this infection may have resulted in papillomatosis of the amniotic epithelium.…”

“…Immunohistochemistry was performed with a rabbit polyclonal anti-E5 antiserum recognizing the C-terminal 14 amino acids of the bovine δPV E5 protein (kind gift of Prof. DiMaio, Yale University School of Medicine, New Haven, CT, USA) and a mouse monoclonal anti-L1 (HPV-16 L1 late protein, Millipore, CA, USA) as previously described [10]. Positive controls were bladder cancer samples where both abortive and productive papillomavirus infection was shown to occur [32].…”

“…In cattle and water buffalo (Bubalus bubalis), they cause cutaneous papillomas and have also been associated with bladder cancer [5][6][7][8][9]. They are the only PVs known to be characterized by a trans-species transmission and infection [1,10]. The bovine δPVs have been associated with sarcoids in horses [11,12], African lions [13], and domestic cats [14].…”

“…The bovine δPVs have been associated with sarcoids in horses [11,12], African lions [13], and domestic cats [14]. Additionally, bovine δPV-2 and δPV-13 have been found to cause congenital oral papillomatosis of the lip in newborn lambs [10]. Bovine δPV DNA has also been detected in a squamous cell carcinoma of head and neck in a Connemara mare [15], in a series of cutaneous spindle cell tumors in horses [16], and in skin lesions of Cape mountain zebras, giraffes, and sable antelopes [17].…”

High Genotypic Diversity, Putative New Types and Intra-Genotype Variants of Bovine Papillomavirus in Northeast Brazil

“…Bovine papillomavirus (BPV) is an oncogenic virus belonging to the Papillomaviridae family, which infects the epithelium and mucosa of many animals including cattle. Although papillomaviruses are usually species-specific, BPV has been observed in other animals such as giraffes, buffalo, sheep and horses [1][2][3][4][5][6][7]. BPVs are classified into five genera and 28 types have been identified so far.…”