Lyon IARC Polyomavirus Displays Transforming Activities in Primary Human Cells

Assunta Venuti, Maria Carmen Romero-Medina, Giusi Melita, Maria Grazia Ceraolo, Rosario Nicola Brancaccio, Cecilia Sirand, Valerio Taverniti, Renske Steenbergen, Tarik Gheit, Massimo Tommasino

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2 Citations (Scopus)


Several studies reported the presence of a recently discovered polyomavirus (PyV), Lyon IARC PyV (LIPyV), in human and domestic animal specimens. LIPyV has some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV (MCPyV), respectively. In this study, we demonstrate that LIPyV early proteins immortalize human foreskin keratinocytes. LIPyV LT binds pRb, accordingly cell cycle checkpoints are altered in primary human fibroblasts and keratinocytes expressing LIPyV early genes. Mutation of the pRb binding site in LT strongly affected the ability of LIPyV ER to induced HFK immortalization. LIPyV LT also binds p53 and alters p53 functions activated by cellular stresses. Finally, LIPyV early proteins activate telomerase reverse transcriptase (hTERT) gene expression, via accumulation of the Sp1 transcription factor. Sp1 recruitment to the hTERT promoter is controlled by its phosphorylation, which is mediated by ERK1 and CDK2. Together, these data highlight the transforming properties of LIPyV in in vitro experimental models, supporting its possible oncogenic nature.
Original languageEnglish
JournalJournal of Virology
Issue number14
Early online date30 Jun 2022
Publication statusPublished - 1 Jul 2022


  • Lyon IARC polyomavirus
  • Sp1 transcription factor
  • cellular transformation
  • hTERT activation
  • p53 and pRb

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