Scientific article
Open access

Rhinovirus genome evolution during experimental human infection

Published inPloS one, vol. 5, no. 5, e10588
Publication date2010

Human rhinoviruses (HRVs) evolve rapidly due in part to their error-prone RNA polymerase. Knowledge of the diversity of HRV populations emerging during the course of a natural infection is essential and represents a basis for the design of future potential vaccines and antiviral drugs. To evaluate HRV evolution in humans, nasal wash samples were collected daily for five days from 15 immunocompetent volunteers experimentally infected with a reference stock of HRV-39. In parallel, HeLa-OH cells were inoculated to compare HRV evolution in vitro. Nasal wash in vivo assessed by real-time PCR showed a viral load that peaked at 48-72 h. Ultra-deep sequencing was used to compare the low-frequency mutation populations present in the HRV-39 inoculum in two human subjects and one HeLa-OH supernatant collected 5 days post-infection. The analysis revealed hypervariable mutation locations in VP2, VP3, VP1, 2C and 3C genes and conserved regions in VP4, 2A, 2B, 3A, 3B and 3D genes. These results were confirmed by classical sequencing of additional samples, both from inoculated volunteers and independent cell infections, and suggest that HRV inter-host transmission is not associated with a strong bottleneck effect. A specific analysis of the VP1 capsid gene of 15 human cases confirmed the high mutation incidence in this capsid region, but not in the antiviral drug-binding pocket. We could also estimate a mutation frequency in vivo of 3.4x10(-4) mutations/nucleotides and 3.1x10(-4) over the entire ORF and VP1 gene, respectively. In vivo, HRV generate new variants rapidly during the course of an acute infection due to mutations that accumulate in hot spot regions located at the capsid level, as well as in 2C and 3C genes.

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Consensus Sequence
  • DNA Mutational Analysis
  • *Evolution, Molecular
  • Genetic Loci/genetics
  • Genome, Viral/*genetics
  • HeLa Cells
  • Humans
  • Kinetics
  • Middle Aged
  • Molecular Sequence Data
  • Mutation/genetics
  • Open Reading Frames/genetics
  • Picornaviridae Infections/*genetics/*virology
  • Rhinovirus/*genetics
  • Viral Load/genetics
  • Viral Proteins/chemistry/genetics
  • Young Adult
Citation (ISO format)
CORDEY, Samuel et al. Rhinovirus genome evolution during experimental human infection. In: PloS one, 2010, vol. 5, n° 5, p. e10588. doi: 10.1371/journal.pone.0010588
Main files (1)
Article (Published version)
ISSN of the journal1932-6203

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