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Intra-patient viral evolution in polyomavirus-related diseases

Dorian McIlroy1,2,3, Franck Halary1,3, Céline Bressollette-Bodin1,4,3,5

  • 11 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes , 44093 Nantes cedex 01 , France.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|April 9, 2019
PubMed

Insights

Human polyomaviruses (PyVs) evolve within a single host, driving diseases like Merkel cell carcinoma and progressive multifocal leukoencephalopathy. This intra-host evolution is key to viral pathogenesis and disease development.

Area of Science:

  • Virology
  • Oncology
  • Molecular Biology

Background:

  • Human polyomaviruses (PyVs) are generally considered genetically stable between hosts.
  • Intra-host molecular evolution is increasingly recognized as a significant factor in PyV infections.
  • This evolution impacts viral pathogenesis and disease progression.

Purpose of the Study:

  • To explore the role of intra-host molecular evolution in human polyomavirus infections.
  • To understand how viral evolution contributes to diseases such as Merkel cell carcinoma (MCC), progressive multifocal leukoencephalopathy (PML), and PyV-associated nephropathy.

Main Methods:

  • Analysis of mutations in the early region of the Merkel cell PyV genome.
  • Investigation of non-coding control region (NCCR) rearrangements and virion protein (VP) 1 mutations in JCPyV and BKPyV.
  • Correlation of viral genetic changes with disease development in the central nervous system and kidneys.

Main Results:

  • Mutations in the Merkel cell PyV early region lead to a truncated large tumour (LT) antigen, crucial for MCC transformation.
  • NCCR rearrangements and VP1 mutations in JCPyV facilitate replication in the central nervous system, causing PML.
  • NCCR rearrangements in BKPyV are linked to increased kidney replication and PyV-associated nephropathy.

Conclusions:

  • Intra-host viral evolution is a critical component in the pathogenesis of multiple human polyomavirus-associated diseases.
  • Understanding these evolutionary mechanisms is essential for developing targeted therapeutic strategies.
  • This research highlights the dynamic nature of viral genomes within infected hosts.
Keywords:
polyomavirusviral evolutionvirulence

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