Human polyomaviruses and papillomaviruses

Discovery, epidemiology, disease association and pathogenicity of HPyV and HPV

Principal investigator

Dr. Mariet C.W. Feltkamp

TSV spiculeDescription of research

Human papillomavirus (HPV) and polyomavirus (HPyV) infections pose a number of serious medical problems, especially in immunocompromised hosts. These include BKPyV-caused nephropathy of kidney transplantation patients, JCPyV-caused progressive multifocal encephalitis of MS patients treated with immunomodulatory drugs such as Natalizumab, and squamous carcinomas of the cervix and skin (HPV). Novel human polyomaviruses, such as TSPyV discovered by our team and MPyCV, cause dysplastic of neoplastic skin diseases, such as trichodysplasia spinulosa and Merkel-cell carcinoma. It is generally believed that there are more HPyVs around to be discovered, especially in immunocompromized hosts. Of most of the recently discovered HPyVs, for instance the New-Jersey polyomavirus, we are unaware of their prevalence and disease associations. Furthermore, their evolutionary spread, route of transmission and tissue tropism are not yet settled, as is true for some of the ‘old’ HPyVs as well. With the use of molecular and serological detection techniques we study the presence of novel and old HPyVs and HPVs in different tissues and (diseased) populations, including solid-organ transplantation patients and healthy blood donors. Furthermore, the expression and role of specific viral products, especially the T-antigens, in cell transformation is studied to identify new leads for HPyV-treatment.

Research Topics

  • Epidemiology of human polyomaviruses and betapapillomaviruses
  • Identification of new human polyomaviruses
  • Prevention of BK polyomavirus-associated nephropathy after kidney transplantation
  • Transforming properties of human polyomaviruses and betapapillomaviruses

Key publications

  • Human papillomavirus and post-transplant cutaneous squamous-cell carcinoma: a multicenter, prospective cohort study. Bouwes Bavinck JN, Feltkamp MCW, Green AC, Fiocco M, Euvrard S, Harwood CA, Proby CM, Naldi L, Diphoorn JCD, Venturuzzo A, Tessari G, Nindl I, Sampogna F, Abeni D, Neale RE, Goeman JJ, Quint KD, Halk AB, Sneek C, Genders RE, de Koning MNC, Quint WGV, Wieland U, Weissenborn S, Waterboer T, Pawlita M, Pfister H; EPI-HPV-UV-CA group. Am J Transplant. 2017 Oct 11
  • Primary polyomavirus infection, not reactivation, as the cause of trichodysplasia spinulosa in immunocompromised patients van der Meijden E, Horváth B, Nijland M, de Vries K, Rácz E, Diercks GF, de Weerd AE, Clahsen-van Groningen MC, van der Blij-Brouwer CS, van der Zon AJ, Kroes AC, Hedman K, van Kampen JJ, Riezebos-Brilman A, Feltkamp MC. J Infect Dis. 2017; 215(7):1080-1084
  • Pretransplantation Donor-Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation. Wunderink HF, van der Meijden E, van der Blij-de Brouwer CS, Mallat MJ, Haasnoot GW, van Zwet EW, Claas EC, de Fijter JW, Kroes AC, Arnold F, Touzé A, Claas FH, Rotmans JI, Feltkamp MC. Am J Transplant. 2017; 17(1):161-172
  • Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa. van der Meijden E, Kazem S, Dargel CA, van Vuren N, Hensbergen PJ, Feltkamp MC. J Virol. 2015 Sep 15;89(18):9427-39.
  • Interspecific adaptation by binary choice at de novo polyomavirus T antigen site through accelerated codon-constrained Val-Ala toggling within an intrinsically disordered region. Lauber C, Kazem S, Kravchenko AA, Feltkamp MC, Gorbalenya AE. Nucleic Acids Res. 2015 May 26;43(10):4800-13.
  • Human Beta-papillomavirus infection and keratinocyte carcinomas. Quint KD, Genders RE, de Koning MN, Borgogna C, Gariglio M, Bouwes Bavinck JN, Doorbar J, Feltkamp MC. J Pathol. 2015 Jan;235(2):342-54.
  • Polyomavirus-associated Trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21. Kazem S, van der Meijden E, Wang RC, Rosenberg AS, Pope E, Benoit T, Fleckman P, Feltkamp MC. PLoS One. 2014 Oct 7;9(10):e108947.
  • Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Rozenblatt-Rosen O, Deo RC, Padi M, Adelmant G, Calderwood MA, Rolland T, Grace M, Dricot A, Askenazi M, Tavares M, Pevzner SJ, Abderazzaq F, Byrdsong D, Carvunis AR, Chen AA, Cheng J, Correll M, Duarte M, Fan C, Feltkamp MC, Ficarro SB, Franchi R, Garg BK, Gulbahce N, Hao T, Holthaus AM, James R, Korkhin A, Litovchick L, Mar JC, Pak TR, Rabello S, Rubio R, Shen Y, Singh S, Spangle JM, Tasan M, Wanamaker S, Webber JT, Roecklein-Canfield J, Johannsen E, Barabási AL, Beroukhim R, Kieff E, Cusick ME, Hill DE, Münger K, Marto JA, Quackenbush J, Roth FP, DeCaprio JA, Vidal M. Nature. 2012 Jul 26;487(7408):491-5.
  • Trichodysplasia spinulosa is characterized by active polyomavirus infection. Kazem S, van der Meijden E, Kooijman S, Rosenberg AS, Hughey LC, Browning JC, Sadler G, Busam K, Pope E, Benoit T, Fleckman P, de Vries E, Eekhof JA, Feltkamp MC. J Clin Virol. 2012; 53:225-30.
  • Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. PLoS Pathog. 2010; 6:e1001024.
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