Rhinovirus genome variation during chronic upper and lower respiratory tract infections

Tapparel, Caroline; Cordey, Samuel; Junier, Thomas; Farinelli, Laurent Luca Denis; Van Belle, Sandra; Gasche-Soccal, Paola Marina Alessandra; Aubert, John-David; Zdobnov, Evgeny; Kaiser, Laurent

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Title		Rhinovirus genome variation during chronic upper and lower respiratory tract infections
Authors		Tapparel, Caroline Cordey, Samuel Junier, Thomas Farinelli, Laurent Luca Denis Van Belle, Sandra Gasche-Soccal, Paola Marina Alessandra Aubert, John-David Zdobnov, Evgeny Kaiser, Laurent show all authors [1 - 9]
Published in		PLOS ONE. 2011, vol. 6, no. 6, p. e21163
Abstract		Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5'UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.
Keywords		Child — Genome, Viral — Genotype — High-Throughput Nucleotide Sequencing — Humans — Molecular Sequence Data — Phylogeny — Picornaviridae Infections/genetics/virology — Respiratory Tract Infections/genetics/virology — Rhinovirus/classification/genetics
Identifiers		DOI: 10.1371/journal.pone.0021163 PMID: 21713005
Full text		Article (Published version) (387 Kb) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research groups		Groupe Laurent Kaiser (virologie clinique) (668) Génétique et biologie moléculaire des infections à Staphylococcus aureus (667) Génomique Evolutionnaire Computationnelle (830) Glycopeptide résistance (28)
Citation (ISO format)		TAPPAREL, Caroline et al. Rhinovirus genome variation during chronic upper and lower respiratory tract infections. In: PLOS ONE, 2011, vol. 6, n° 6, p. e21163. https://archive-ouverte.unige.ch/unige:25859