An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides.
Fiche publication
Date publication
octobre 2018
Journal
PLoS pathogens
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Dr CARAPITO Raphaël
Tous les auteurs :
Domingo-Calap P, Schubert B, Joly M, Solis M, Untrau M, Carapito R, Georgel P, Caillard S, Fafi-Kremer S, Paul N, Kohlbacher O, González-Candelas F, Bahram S
Lien Pubmed
Résumé
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.
Mots clés
Amino Acid Substitution, BK Virus, genetics, Genome, Viral, HLA-C Antigens, genetics, High-Throughput Nucleotide Sequencing, Humans, Mutation, Organ Transplantation, Peptide Fragments, genetics, Phylogeny, Polyomavirus Infections, genetics
Référence
PLoS Pathog.. 2018 Oct 18;14(10):e1007368