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PLoS Pathog. 2018 Oct 18;14(10):e1007368. doi: 10.1371/journal.ppat.1007368. eCollection 2018 Oct.

An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides.

Author information

1
Plateforme GENOMAX, Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
2
Fédération Hospitalo-Universitaire, OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, Strasbourg, France.
3
Center for Bioinformatics, University of Tübingen, Tübingen, Germany.
4
Applied Bioinformatics, Department of Computer Science, Tübingen, Germany.
5
Service de Néphrologie et Transplantation Rénale, Hôpitaux Universitaires de Strasbourg, France.
6
Laboratoire de Virologie, Plateau Technique de Microbiologie, Pôle de Biologie, Hôpitaux Universitaires de Strasbourg, France.
7
Laboratoire Central d'Immunologie, Plateau Technique de Biologie, Nouvel Hôpital Civil, France.
8
Quantitative Biology Center, Tübingen, Germany.
9
Faculty of Medicine, University of Tübingen, Tübingen, Germany.
10
Biomolecular Interactions, Max Planck Institute for Developmental Biology, Tübingen, Germany.
11
Institute for Translational Bioinformatics, University Hospital Tübingen, Tübingen, Germany.
12
Unidad Mixta Infección y Salud Pública FISABIO/Universitat de València, Institute for Integrative Systems Biology I2SysBio (CSIC-UV) and CIBER en Epidemiología y Salud Pública, Valencia, Spain.

Abstract

Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(-3)-10(-5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.

PMID:
30335851
PMCID:
PMC6207329
DOI:
10.1371/journal.ppat.1007368
[Indexed for MEDLINE]
Free PMC Article

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