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Human papillomavirus research: Do we still need animal models?

2009; Wiley; Volume: 125; Issue: 3 Linguagem: Inglês

10.1002/ijc.24430

1097-0215

Giuseppe Borzacchiello, Franco Roperto, Lubna Nasir, M. Saveria Campo,

Infectious Diseases and Mycology

International Journal of CancerVolume 125, Issue 3 p. 739-740 Letter to the EditorFree Access Human papillomavirus research: Do we still need animal models? Giuseppe Borzacchiello, Corresponding Author Giuseppe Borzacchiello [email protected] Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, 80137 Naples, ItalyDepartment of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, Via F. Delpino, 1, 80137 Naples, ItalySearch for more papers by this authorFranco Roperto, Franco Roperto Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, 80137 Naples, ItalySearch for more papers by this authorLubna Nasir, Lubna Nasir Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Garscube Campus, Glasgow G61 1QH, Scotland, United KingdomSearch for more papers by this authorM. Saveria Campo, M. Saveria Campo Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Garscube Campus, Glasgow G61 1QH, Scotland, United KingdomSearch for more papers by this author Giuseppe Borzacchiello, Corresponding Author Giuseppe Borzacchiello [email protected] Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, 80137 Naples, ItalyDepartment of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, Via F. Delpino, 1, 80137 Naples, ItalySearch for more papers by this authorFranco Roperto, Franco Roperto Department of Pathology and Animal Health, Faculty of Veterinary Medicine, University of Naples Federico II, 80137 Naples, ItalySearch for more papers by this authorLubna Nasir, Lubna Nasir Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Garscube Campus, Glasgow G61 1QH, Scotland, United KingdomSearch for more papers by this authorM. Saveria Campo, M. Saveria Campo Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Garscube Campus, Glasgow G61 1QH, Scotland, United KingdomSearch for more papers by this author First published: 19 March 2009 https://doi.org/10.1002/ijc.24430Citations: 14AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Dear Sir, Papillomaviruses (PVs) are nonenveloped DNA viruses that are tumorigenic to humans and numerous animal species.1 Human PVs (HPVs) are of great medical importance because high-risk HPV types, primarily HPV-16 and HPV-18, are the causative agents of cancer. The most important and best documented HPV-associated cancer is cervical carcinoma, with which HPV is associated in more than 90% of cases.2-4 Much of our understanding of PVs, their life cycle and other relevant aspects of pathogenesis has derived from studies of animal PVs as early as the beginning of last century. Bovine PV (BPV), cotton-tail rabbit PV and canine oral PV have been extensively studied and all have contributed to the elucidation of PV pathogenesis.5 Although these three systems have been exceedingly useful models in understanding the oncogenic potential of the virus, the relationship between virus and cofactors, and the development of antiviral vaccines, the explosion of research on HPV and, more recently, the availability of the anti-HPV prophylactic vaccines have generated the widespread belief that PV research is on the wane and animal models are no more needed. In this letter we will argue that this is not the case and that animal PVs still provide new avenues of research. Although this is so for all animal PVs aforementioned, we will focus specifically on new facets of BPV infection and pathogenesis which have come to light, or have been confirmed recently in bovids and equids.6, 7 These are as follows: the association of BPV with lymphoepithelial, vascular and other mesenchymal tumors in cattle8; cross-species infection by BPV in equids with induction of sarcoids,7 and in buffalo and bison with induction of warts9, 10; elucidation of the molecular mechanisms of the oncoprotein E5 in vivo11, 12; the presence and expression of BPV DNA in blood cells of both cattle and horses and its possible role in virus transmission and spreading13, 14; and the association of BPV and inflammation.15 Do these observations point to new opportunities in HPV research? Although BPV infection of species other than Bos is the only documented instance of natural cross-species infection, it is unlikely that this is a single occurrence and anecdotal or single reports of BPV infection in humans handling infected cattle, or of HPV infection in domestic animals, should be investigated. Can HPV infect nonepithelial tissues? Approximately a decade ago, the first reports of the presence of HPV DNA in blood cells of patients proved controversial; the now accepted presence of BPV DNA and of BPV E5 protein in blood cells of cattle and horses should stimulate new interest in similar investigations in humans, especially concerning the role of viral sequences in blood cells. Additionally, a recent article confirmed that, like BPV, HPV can infect vascular tissue,16 and these studies should be expanded to confirm the generality of this observation. The importance of chronic inflammation in oncogenesis is a subject of intense investigation. Although the infectious cycle of PV does not induce inflammation, inflammation is a potential cofactor of PV-associated disease.17, 18 The presence of BPV genomes and, more importantly, the expression of the viral oncogenes in equine inflammatory skin conditions suggest that BPV is more than a passive passenger in the disease. These observations provide the opportunity to study experimentally the relationship between a PV, cell proliferation, antigen stimulation, chronic inflammation, disease and potential tumor progression. Comparative oncology contributes to the understanding of human cancer. The study of PV pathogenesis has benefited and continues to do so from investigations in animal models. In conclusion, if we ask ourselves whether there is still a need for animal models of PV—yes must be the only answer. Yours sincerely, References 1 IARC. IARC monographs on the evaluation of carcinogenic risks to humans, vol. 90: human papillomaviruses. Lyon: WHO/IARC, 2007. 2 Bosch FX,Munoz N. The viral etiology of cervical cancer. Virus Res 2002; 89: 183– 90. 3 Munoz N,Bosch FX,Castellsagué X,Díaz M,de Sanjose S,Hammouda D,Shah KV,Meijer CJ. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004; 111: 278– 85. 4 Walboomers JM,Jacobs MV,Manos MM,Bosch FX,Kummer JA,Shah KV,Snijders PJ,Peto J,Meijer CJ,Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 12– 19. 5 Campo MS. Animal models of papillomavirus pathogenesis. Virus Res 2002; 89: 249– 61. 6 Campo MS. Bovine papillomavirus: old system new lesson? In: MS Campo, ed. Papillomavirus research from natural history to vaccines and beyond. Norfolk: Caister Academic Press, 2006. 373– 87. 7 Nasir L,Campo MS. Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids. Vet Dermatol 2008; 19: 243– 54. 8 Borzacchiello G,Russo V,Spoleto C,Roperto S,Balcos L,Rizzo C,Venuti A,Roperto F. Bovine papillomavirus type-2 DNA and expression of E5 and E7 oncoproteins in vascular tumours of the urinary bladder in cattle. Cancer Lett 2007; 250: 82– 9. 9 Silvestre O,Borzacchiello G,Nava D,Iovane G,Russo V,Vecchio D,D'Ausilio F,Paciello O. Bovine papillomavirus type 1 DNA and E5 oncoprotein expression in water buffaloes fibropapillomas. Vet Pathol 2009 Mar. 9 [Epub ahead of print]. 10 Literák I,Tomita Y,Ogawa T,Shirasawa H,Smíd B,Novotny L,Adamec M. Papillomatosis in a European Bison. J Wildl Dis 2006; 42: 149– 53. 11 Araibi EH,Marchetti B,Ashrafi GH,Campo MS. Downregulation of major histocompatibility complex class I in bovine papillomas. J Gen Virol 2004; 85: 2809– 14. 12 Borzacchiello G,Russo V,Gentile F,Roperto F,Venuti A,Nitsch L,Campo MS,Roperto S. Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor β receptor in naturally occurring bovine urinary bladder tumours. Oncogene 2006; 25: 1251– 60. 13 Roperto S,Brun R,Paolini F,Urraro C,Russo V,Borzacchiello G,Pagnini U,Raso C,Rizzo C,Roperto F,Venuti A. Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role. J Gen Virol 2008; 89: 3027– 33. 14 Brandt S,Haralambus R,Schoster A,Kirnbauer R,Stanek C. Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines. J Gen Virol 2008; 89: 1390– 95. 15 Yuan Z,Philbey AW,Gault EA,Campo MS,Nasir L. Detection of bovine papillomavirus type 1 genomes and viral gene expression in equine inflammatory skin conditions. Virus Res 2007; 124: 245– 9. 16 Füle T,Máthé M,Suba Z,Csapó Z,Szarvas T,Tátrai P,Paku S,Kovalszky I. The presence of human papillomavirus 16 in neural structures and vascular endothelial cells. Virology 2006; 348: 289– 96. 17 Favre M,Orth G,Majewski S,Baloul S,Pura A,Jablonska S. Psoriasis: a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis. J Invest Dermatol 1998; 110: 311– 17. 18 Simeone P,Teson M,Latini A,Carducci M,Venuti A. Human papillomavirus type 5 in primary keratinocytes from psoriatic skin. Exp Dermatol 2005; 14: 824– 29. Giuseppe Borzacchiello, Franco Roperto, Lubna Nasir, M. Saveria Campo. Citing Literature Volume125, Issue31 August 2009Pages 739-740 ReferencesRelatedInformation