6533b852fe1ef96bd12ab73e

RESEARCH PRODUCT

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

Pilar Domingo-calapBenjamin SchubertMélanie JolyMorgane SolisMeiggie UntrauRaphael CarapitoPhilippe GeorgelSophie CaillardSamira Fafi-kremerNicodème PaulOliver KohlbacherFernando González-candelasSeiamak Bahram

subject

RNA viruses0301 basic medicineMutation ratePhysiologyvirusesUrinePathology and Laboratory Medicinemedicine.disease_causeBiochemistryMedicine and Health SciencesBiology (General)Amino AcidsGenome EvolutionPhylogenyData ManagementMutationOrganic CompoundsHigh-Throughput Nucleotide SequencingPhylogenetic AnalysisDNA virusGenomicsBody FluidsBK virusPhylogeneticsChemistryMedical MicrobiologyViral PathogensViral evolutionVirusesPhysical SciencesEvolutionary RatePathogensAnatomyResearch ArticleComputer and Information SciencesEvolutionary ProcessesQH301-705.5ImmunologyGenome ViralHLA-C AntigensBiologyMicrobiologyMolecular EvolutionViral EvolutionVirusDeep sequencing03 medical and health sciencesVirologyGeneticsmedicineHumansEvolutionary SystematicsMicrobial PathogensMolecular BiologyTaxonomyEvolutionary BiologyPolyomavirus InfectionsOrganic ChemistryOrganismsChemical CompoundsBiology and Life SciencesComputational BiologyProteinsOrgan TransplantationRC581-607030112 virologyVirologyOrganismal EvolutionPeptide FragmentsPolyomaviruses030104 developmental biologyAmino Acid SubstitutionBK VirusMicrobial EvolutionMutationParasitologyImmunologic diseases. AllergyDNA virusesPolyomavirus Infections

description

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.

10.13039/501100011033http://hdl.handle.net/10261/184271