Metagenomic discovery of 83 new human papillomavirus types in patients with immunodeficiency

Diana V. Pastrana, Alberto Peretti, Nicole L. Welch, Cinzia Borgogna, Carlotta Olivero, Raffaele Badolato, Lucia D. Notarangelo, Marisa Gariglio, Peter C. FitzGerald, Carl E. McIntosh, Jesse Reeves, Gabriel J. Starrett, Valery Bliskovsky, Daniel Velez, Isaac Brownell, Robert Yarchoan, Kathleen M. Wyvill, Thomas S. Uldrick, Frank Maldarelli, Andrea LiscoIrini Sereti, Christopher M. Gonzalez, Elliot J. Androphy, Alison A. McBride, Koenraad Van Doorslaer, Francisco Garcia, Israel Dvoretzky, Joceline S. Liu, Justin Han, Philip M. Murphy, David H. McDermott, Christopher B. Buck

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Several immunodeficiencies are associated with high susceptibility to persistent and progressive human papillomavirus (HPV) infection leading to a wide range of cutaneous and mucosal lesions. However, the HPV types most commonly associated with such clinical manifestations in these patients have not been systematically defined. Here, we used virion enrichment, rolling circle amplification, and deep sequencing to identify circular DNA viruses present in skin swabs and/or wart biopsy samples from 48 patients with rare genetic immunodeficiencies, including patients with warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, or epidermodysplasia verruciformis (EV). Their profiles were compared with the profiles of swabs from 14 healthy adults and warts from 6 immunologically normal children. Individual patients were typically infected with multiple HPV types; up to 26 different types were isolated from a single patient (multiple anatomical sites, one time point). Among these, we identified the complete genomes of 83 previously unknown HPV types and 35 incomplete genomes representing possible additional new types. HPV types in the genus Gammapapillomavirus were common in WHIM patients, whereas EV patients mainly shed HPVs from the genus Betapapillomavirus. Preliminary evidence based on three WHIM patients treated with plerixafor, a leukocyte mobilizing agent, suggest that longer-term therapy may correlate with decreased HPV diversity and increased predominance of HPV types associated with childhood skin warts.

Original languageEnglish (US)
Article numbere00645-18
Issue number6
StatePublished - Nov 1 2018


  • Epidermodysplasia verruciformis
  • Gammapapillomaviruses
  • Metagenomic
  • Next-generation sequencing
  • Plerixafor
  • Skin swabs
  • WHIM syndrome

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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