Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent.

-Bovine papillomaviruses (BPV) are DNA oncogenic viruses inducing hyperplastic benign lesions of both cutaneous and mucosal epithelia in cattle. Ten (BPV 1-10) different viral genotypes have been characterised so far. BPV 1-10 are all strictly species-specific but BPV 1/2 may also infect equids inducing fibroblastic tumours. These benign lesions generally regress but may also occasionally persist, leading to a high risk of evolving into cancer, particularly in the presence of environmental carcinogenic co-factors. Among these, bracken fern is the most extensively studied. The synergism between immunosuppressants and carcinogenic principles from bracken fern and the virus has been experimentally demonstrated for both urinary bladder and alimentary canal cancer in cows whose diets were based on this plant. BPV associated tumours have veterinary and agricultural relevance in their own right, although they have also been studied as a relevant model of Human papillomavirus (HPV). Recent insights into BPV biology have paved the way to new fields of speculation on the role of these viruses in neoplastic transformation of cells other than epithelial ones. This review will briefly summarise BPV genome organization, will describe in greater detail the functions of viral oncoproteins, the interaction between the virus and co-carcinogens in tumour development; relevant aspects of immunity and vaccines will also be discussed.

Bovine papillomavirus type 2 (BPV-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. In this study, we investigated the simultaneous presence of BPV-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating BPV-2. Peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. Circulating BPV-2 DNA was detected in 61 of them and in two blood samples from healthy cows. Fifty of the affected animals were slaughtered at public slaughterhouses and neoplastic proliferations in the urinary bladder were detected in all of them. BPV-2 DNA was amplified and sequenced in 78 % of urinary bladder tumour samples and in 38.9 % of normal samples as a control. Circulating episomal BPV-2 DNA was detected in 78.2 % of the blood samples. Simultaneous presence of BPV-2 DNA in neoplastic bladder and blood samples was detected in 37 animals. Specific viral E5 mRNA and E5 oncoprotein were also detected in blood by RT-PCR and Western blot/immunocytochemistry, respectively. It is likely that BPV-2 can persist and be maintained in an active status in the bloodstream, in particular in the lymphocytes, as a reservoir of viral infection that, in the presence of co-carcinogens, may cause the development of urinary bladder tumours. INTRODUCTIONBovine papillomaviruses (BPVs) are species-specific, double-stranded DNA viruses responsible for cutaneous and mucosal neoplastic lesions. They are small non-enveloped viruses with an icosahedral capsid. Their open reading frames (ORFs) are divided into early (E) and late (L) regions. The early region encodes non-structural proteins E1 to E7, of which, E5, E6 and E7 are known to be oncoproteins. The late region encodes structural proteins L1 and L2 forming the capsid. Bovine papillomavirus type 2 (BPV-2) is classified in the genus Deltapapillomavirus, species 4, the biological properties of which are characterized by the induction of fibropapillomas in cattle and sarcoids in equids (Brandt et al., 2008;Chambers et al., 2003;de Villiers et al., 2004). BPV-2 infection in the presence of environmental carcinogens, such as ptaquiloside (PT) of bracken fern (Pteridium aquilinum), has been associated with urinary bladder neoplastic lesions in adult cattle, in which chronic enzootic haematuria (CEH) is the most important clinical sign (Campo, 1997; Campo et al., 1992;Hopkins, 1986).The effect of the route of viral infection, and the synergistic relationship between BPV-2 and immunosuppressive and oncogenic compounds present in the bracken fern in the malignant progression of bladder lesions (Campo, 1997; Campo et al., 1992; Jarrett et al., 1978;Reddy & Fialkow, 1983;Stocco dos Santos et al., 1998) are not well-known, thus deserving further investigations.To date, the BPV-2 genome has been detected in lymphocytes during latent papillomavirus infection in cattle (Campo et al., 1994). In addition, the occurrence of horiz...

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting in upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC.

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