1887

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Volume 92, Issue 8

PBMCs are additional sites of productive infection of bovine papillomavirus type 2 Free

Abstract

Bovine papillomavirus type 2 (BPV-2) is an oncogenic virus infecting both epithelial and mesenchymal cells. Its life cycle, similar to other papillomaviruses (PVs), appears to be linked to epithelial differentiation. Human and bovine PVs have been known to reside in a latent, episomal form in PBMCs; therefore, it is believed that blood cells, like all mesenchymal cells, function as non-permissive carriers. Here, for the first time in veterinary and comparative medicine, the BPV-2 E5 oncoprotein and the major structural L1 capsid protein, known to be expressed only in productive infections, were shown to occur in defined subsets of PBMCs. E5 oncoprotein was detected in sorted T- and B-cells as well as in monocytes by flow cytometry and Western blot analysis. However, CD4 and CD8 lymphocytes appeared to be the main circulating targets of the virus, thus possibly representing the most important reservoir of active BPV-2 in blood. L1 protein was identified by flow cytometry in a population of blood cells recognized as lymphocytes by morphological scatter properties. Western blot analysis was performed on lysates obtained from the sorted subpopulations of PBMCs and detected L1 protein in CD4 and CD8 cells only. Thus, this study showed that CD4 and CD8 lymphocytes are permissive for BPV-2 and are new, hitherto unknown sites of productive PV infection. In light of these observations, the life cycle of PVs needs to be revisited to gain novel insights into the epidemiology of BPV infection and the pathogenesis of related diseases.

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© 2011 SGM
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2011-08-01
2024-04-16
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References

  1. Balcos L. G. F., Borzacchiello G., Russo V., Popescu G., Roperto S., Roperto F. 2008; Association of bovine papillomavirus type-2 and urinary bladder tumours in cattle from Romania. Res Vet Sci 85:145–148 [CrossRef]
     [Google Scholar]
  2. Bodaghi S., Wood L. V., Roby G., Ryder C., Steinberg S. M., Zheng Z.-M. 2005; Could human papillomaviruses be spread through blood?. J Clin Microbiol 43:5428–5434 [View Article][PubMed]
     [Google Scholar]
  3. Borzacchiello G., Roperto F. 2008; Bovine papillomaviruses, papillomas and cancer in cattle. Vet Res 39:45–63 [View Article][PubMed]
     [Google Scholar]
  4. Borzacchiello G., Iovane G., Marcante M. L., Poggiali F., Roperto F., Roperto S., Venuti A. 2003; Presence of bovine papillomavirus type 2 DNA and expression of the viral oncoprotein E5 in naturally occurring urinary bladder tumours in cows. J Gen Virol 84:2921–2926 [View Article][PubMed]
     [Google Scholar]
  5. Borzacchiello G., Roperto F., Nasir L., Campo M. S. 2009; Human papillomavirus research: do we still need animal models?. Int J Cancer 125:739–740 [View Article][PubMed]
     [Google Scholar]
  6. Brandt S., Haralambus R., Schoster A., Kirnbauer R., Stanek C. 2008; Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines. J Gen Virol 89:1390–1395 [View Article][PubMed]
     [Google Scholar]
  7. Campo M. S. 2006; Bovine papillomavirus: old system, new lessons?. In Papillomavirus Research – from Natural History to Vaccines and Beyond pp. 373–387 Edited by Campo S. Norfolk, UK: Caister Academic Press;
     [Google Scholar]
  8. Campo M. S., Jarrett W. F. H., O’Neil W., Barron R. J. 1994; Latent papillomavirus infection in cattle. Res Vet Sci 56:151–157 [View Article][PubMed]
     [Google Scholar]
  9. Carlson G. P., Kaneko J. J. 1973; Isolation of leukocytes from bovine peripheral blood. Proc Soc Exp Biol Med 142:853–856[PubMed] [CrossRef]
     [Google Scholar]
  10. Castellsagué X., Drudis T., Cañadas M. P., Goncé A., Ros R., Pérez J. M., Quintana M. J., Muñoz J., Albero G. et al. 2009; Human papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain. BMC Infect Dis 9:74–85 [View Article][PubMed]
     [Google Scholar]
  11. Chambers G., Ellsmore V. A., O’Brien P. M., Reid S. W., Love S., Campo M. S., Nasir L. 2003; Association of bovine papillomavirus with the equine sarcoid. J Gen Virol 84:1055–1062 [View Article][PubMed]
     [Google Scholar]
  12. Chen A. C.-H., Keleher A., Kedda M.-A., Spurdle A. B., McMillan N. A. J., Antonsson A. 2009; Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors. J Med Virol 81:1792–1796 [View Article][PubMed]
     [Google Scholar]
  13. de Villiers E.-M., Fauquet C., Broker T. R., Bernard H.-U., zur Hausen H. 2004; Classification of papillomaviruses. Virology 324:17–27 [View Article][PubMed]
     [Google Scholar]
  14. Füle T., Máthé M., Suba Z., Csapó Z., Szarvas T., Tátrai P., Paku S., Kovalszky I. 2006; The presence of human papillomavirus 16 in neural structures and vascular endothelial cells. Virology 348:289–296 [View Article][PubMed]
     [Google Scholar]
  15. Ho C.-M., Yang S.-S., Chien T.-Y., Huang S.-H., Jeng C.-J., Chang S.-F. 2005; Detection and quantitation of human papillomavirus type 16, 18 and 52 DNA in the peripheral blood of cervical cancer patients. Gynecol Oncol 99:615–621 [View Article][PubMed]
     [Google Scholar]
  16. IARC 2007 Monographs on the Evaluation of Carcinogenic Risks to Humans. Human Papillomaviruses vol. 90 Lyon: IARC Press;
     [Google Scholar]
  17. Literák I., Tomita Y., Ogawa T., Shirasawa H., Smíd B., Novotny L., Adamec M. 2006; Papillomatosis in a European bison. J Wildl Dis 42:149–153[PubMed] [CrossRef]
     [Google Scholar]
  18. Maxie M. G. 1993; The urinary system. In Pathology of Domestic Animals, 4th edn. pp. 534–536 Edited by Jubb K. V. F., Kennedy P. C., Palmer N. San Diego: Academic Press;
     [Google Scholar]
  19. Moody C. A., Laimins L. A. 2010; Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10:550–560 [View Article][PubMed]
     [Google Scholar]
  20. Munday J. S., Knight C. G. 2010; Amplification of feline sarcoid-associated papillomavirus DNA sequences from bovine skin. Vet Dermatol 21:341–344[PubMed] [CrossRef]
     [Google Scholar]
  21. Orbell G. M., Young S., Munday J. S. 2010; Cutaneous sarcoids in captive African lions associated with feline sarcoid-associated papillomavirus infection. Vet Pathol (Epub ahead of print) [View Article][PubMed]
     [Google Scholar]
  22. Pamukcu A. M., Price J. M., Bryan G. T. 1976; Naturally occurring and bracken fern-induced bovine urinary bladder tumors. Vet Pathol 13:110–122[PubMed]
     [Google Scholar]
  23. Pao C. C., Hor J. J., Yang F. P., Lin C.-Y., Tseng C. J. 1997; Naturally occurring and braken-fern-induced bovine urinary bladder tumors. Clinical and morphological characteristics. J Clin Oncol 15:1008–1012[PubMed]
     [Google Scholar]
  24. Roperto S., Brun R., Paolini F., Urraro C., Russo V., Borzacchiello G., Pagnini U., Raso C., Rizzo C. et al. 2008; Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role. J Gen Virol 89:3027–3033 [View Article][PubMed]
     [Google Scholar]
  25. Roperto S., Borzacchiello G., Brun R., Leonardi L., Maiolino P., Martano M., Paciello O., Papparella S., Restucci B., other authors. 2010a; A review of bovine urothelial tumours and tumour-like lesions of the urinary bladder. J Comp Pathol 142:95–108 [View Article][PubMed]
     [Google Scholar]
  26. Roperto S., Borzacchiello G., Brun R., Costanzo F., Faniello M. C., Raso C., Rosati A., Russo V., Leonardi L., other authors. 2010b; Ferritin heavy chain (FHC) is up-regulated in papillomavirus-associated urothelial tumours of the urinary bladder in cattle. J Comp Pathol 142:9–18 [View Article][PubMed]
     [Google Scholar]
  27. Roperto S., Colabufo N. A., Inglese C., Urraro C., Brun R., Mezza E., Staibano S., Raso C., Maiolino P., other authors. 2010c; Sigma-2 receptor expression in bovine papillomavirus-associated urinary bladder tumours. J Comp Pathol 142:19–26 [View Article][PubMed]
     [Google Scholar]
  28. Sarkola M. E., Grénman S. E., Rintala M. A. M., Syrjänen K. J., Syrjänen S. M. 2008; Human papillomavirus in the placenta and umbilical cord blood. Acta Obstet Gynecol Scand 87:1181–1188 [View Article][PubMed]
     [Google Scholar]
  29. Shafti-Keramat S., Schellenbacher C., Handisurya A., Christensen N., Reininger B., Brandt S., Kirnbauer R. 2009; Bovine papillomavirus type 1 (BPV1) and BPV2 are closely related serotypes. Virology 393:1–6 [View Article][PubMed]
     [Google Scholar]
  30. Silvestre O., Borzacchiello G., Nava D., Iovane G., Russo V., Vecchio D., D’Ausilio F., Gault E. A., Campo M. S., Paciello O. 2009; Bovine papillomavirus type 1 DNA and E5 oncoprotein expression in water buffalo fibropapillomas. Vet Pathol 46:636–641 [View Article][PubMed]
     [Google Scholar]
  31. Stocco dos Santos R. C., Lindsey C. J., Ferraz O. P., Pinto J. R., Mirandola R. S., Benesi F. J., Birgel E. H., Pereira C. A., Beçak W. 1998; Bovine papillomavirus transmission and chromosomal aberrations: an experimental model. J Gen Virol 79:2127–2135[PubMed]
     [Google Scholar]
  32. Syrjänen S. 2010; Current concepts on human papillomavirus infections in children. APMIS 118:494–509 [View Article][PubMed]
     [Google Scholar]
  33. Tomita Y., Literak I., Ogawa T., Jin Z., Shirasawa H. 2007; Complete genomes and phylogenetic positions of bovine papillomavirus type 8 and a variant type from a European bison. Virus Genes 35:243–249 [View Article][PubMed]
     [Google Scholar]
  34. Trenfield K., Spradbrow P. B., Vanselow B. 1985; Sequences of papillomavirus DNA in equine sarcoids. Equine Vet J 17:449–452 [View Article][PubMed]
     [Google Scholar]
  35. Tseng C.-J., Pao C. C., Lin J.-D., Soong Y.-K., Hong J.-H., Hsueh S. 1999; Detection of human papillomavirus types 16 and 18 mRNA in peripheral blood of advanced cervical cancer patients and its association with prognosis. J Clin Oncol 17:1391–1396[PubMed]
     [Google Scholar]
  36. Weismann P., Weismanova E., Masak L., Mlada K., Keder D., Ferancikova Z., Vizvaryova M., Konecny M., Zavodna K. et al. 2009; The detection of circulating tumor cells expressing E6/E7 HR-HPV oncogenes in peripheral blood in cervical cancer patients after radical hysterectomy. Neoplasma 56:230–238 [View Article][PubMed]
     [Google Scholar]
  37. Widschwendter A., Blassnig A., Wiedemair A., Müller-Holzner E., Müller H. M., Marth C. 2003; Human papillomavirus DNA in sera of cervical cancer patients as tumor marker. Cancer Lett 202:231–239 [View Article][PubMed]
     [Google Scholar]
  38. Wosiacki S. R., Barreiro M. A. B., Alfieri A. F., Alfieri A. A. 2005; Semi-nested PCR for detection and typing of bovine papillomavirus type 2 in urinary bladder and whole blood from cattle with enzootic haematuria. J Virol Methods 126:215–219 [CrossRef]
     [Google Scholar]
  39. You H., Liu Y., Agrawal N., Prasad C. K., Edwards J. L., Osborne A. F., Korourian S., Lowery C. L., Hermonat P. L. 2008; Multiple human papillomavirus types replicate in 3A trophoblasts. Placenta 29:30–38 [View Article][PubMed]
     [Google Scholar]
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PBMCs are additional sites of productive infection of bovine papillomavirus type 2
J. Gen. Virol. 92, 1787 (2011); https://doi.org/10.1099/vir.0.031740-0
/content/journal/jgv/10.1099/vir.0.031740-0
/content/journal/jgv/10.1099/vir.0.031740-0
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