Bovine papillomavirus E5 and E7 oncoproteins in naturally occurring tumors: are two better than one?

Abstract

Bovine papillomaviruses (BPVs) are oncogenic DNA viruses, which mainly induce benign lesions of cutaneous and/or mucosal epithelia in cattle. Thirteen (BPV 1–13) different viral genotypes have been characterized so far. BPVs are usually species-specific but BPV 1/2 may also infect equids as well as buffaloes and bison and cause tumors in these species. BPV-induced benign lesions usually regress, however occasionally they develop into cancer particularly in the presence of environmental carcinogenic co-factors. The major transforming protein of BPV is E5, a very short hydrophobic, transmembrane protein with many oncogenic activities. E5 contributes to cell transformation through the activation of the cellular β receptor for the platelet-derived growth factor (PDGFβ-r), it also decreases cell surface expression of major histocompatibility complex class I (MHCI) causing viral escape from immunosurveillance, and plays a role in the inhibition of the intracellular communication by means of aberrant connexin expression. E7 is considered as a weak transforming gene, it synergies with E5 in cell transformation during cancer development. E7 expression correlates in vivo with the over-expression of β1-integrin, which plays a role in the regulation of keratinocytes proliferation and differentiation. Additionally, E7 is involved in cell-mediated immune responses leading to tumour rejection, in anoikis process by direct binding to p600, and in invasion process by upregulation of Matrix metalloproteinase1 (MMP-1) expression. Studies on the role of BPV E5 and E7 oncoproteins in naturally occurring tumours are of scientific value, as they may shed new light on the biological role of these two oncogenes in cell transformation.

Genetic characterization of Amazonian bovine papillomavirus reveals the existence of four new putative types

“…The histopathological findings of the samples are consistent with those lesions typically observed in papilloma lesions [17,24,25] but no fibroblast proliferation was observed, ergo clinical and histopathological findings confirmed the diagnosis of papillomatosis. The majority of the strains clustered within the Deltapapillomavirus genus that encompasses the BPV types considered to be etiological agents of papillomatosis in cattle [12,13,17,18], sarcoid disease in horses [4,5,26], as well as urinary bladder in cow [27]. BPVs 1 and 2 are the most common BPV types distributed worldwide and unusually, they have the ability to infect not only bovines but also other species such as equines [4,5,26], yaks [28], and buffalos [27,29].…”

“…The majority of the strains clustered within the Deltapapillomavirus genus that encompasses the BPV types considered to be etiological agents of papillomatosis in cattle [12,13,17,18], sarcoid disease in horses [4,5,26], as well as urinary bladder in cow [27]. BPVs 1 and 2 are the most common BPV types distributed worldwide and unusually, they have the ability to infect not only bovines but also other species such as equines [4,5,26], yaks [28], and buffalos [27,29]. In Brazil, these BPV types were already described in studies carried out in cattle herds from the Southern, South-East and North-East regions [13,18,30,31], and the present findings reveals that they are also present in the Amazon region of Brazil.…”

Viral Miniproteins

“…The papillomaviruses are small DNA viruses that infect humans and a wide variety of animals, with human papillomaviruses (HPV) being responsible for ∼5% of all human cancers. BPV type 1 and related fibropapillomaviruses from other ungulate species (e.g., pigs and sheep) encode a small, hydrophobic E5 protein and cause skin warts or papillomas with a prominent fibroblastic component (in contrast to the HPV, which induce purely epithelial papillomas) (20, 103a). Only 43 or 44 amino acids long, all fibropapillomavirus E5 proteins share an extremely hydrophobic central portion that serves as a transmembrane domain, a glutamine at position 17, an aspartic acid or glutamic acid at position 33, and two cysteines near the carboxy terminus that stabilize homodimer formation between two E5 monomers (21).…”

Molecular Epidemiology of Bovine Papillomatosis and Identification of Three Genotypes in Central Iraq

“…BPV-induced benign lesions regress spontaneously; however, they may develop into cancer, especially in the presence of cofactors such as environmental carcinogens [19]. BPV diagnosis usually includes a clinical examination, histopathology, and immunohistochemistry [20,21].…”