Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

Hayley Cassidy, Leonard Schuele, Erley Lizarazo-Forero, Natacha Couto, John W.A. Rossen, Alex W. Friedrich, Coretta Van Leer-Buter, Hubert G.M. Niesters

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10-3 substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient.

    Original languageEnglish
    Article numberveab109
    JournalVirus Evolution
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 18 Mar 2022

    Keywords

    • chronic infection
    • enterovirus
    • immunocompromised
    • intra-host evolution
    • nanopore sequencing
    • virus evolution

    ASJC Scopus subject areas

    • Microbiology
    • Virology

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