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- Title
Whole-Genome Next-Generation Sequencing to Study Within-Host Evolution of Norovirus (NoV) Among Immunocompromised Patients With Chronic NoV Infection.
- Authors
van Beek, Janko; de Graaf, Miranda; Smits, Saskia; Schapendonk, Claudia M. E.; Verjans, Georges M. G. M.; Vennema, Harry; van der Eijk, Annemiek A.; Phan, My V. T.; Cotten, Matthew; Koopmans, Marion
- Abstract
<bold>Background: </bold>The genus Norovirus comprises large genetic diversity, and new GII.4 variants emerge every 2-3 years. It is unknown in which host these new variants originate. Here we study whether prolonged shedders within the immunocompromised population could be a reservoir for newly emerging strains.<bold>Methods: </bold>Sixty-five fecal samples from 16 immunocompromised patients were retrospectively selected. Isolated viral RNA was enriched by hybridization with a custom norovirus whole-genome RNA bait set and deep sequenced on the Illumina MiSeq platform.<bold>Results: </bold>Patients shed virus for average 352 days (range, 76-716 days). Phylogenetic analysis showed distinct GII.4 variants in 3 of 13 patients (23%). The viral mutation rates were variable between patients but did not differ between various immune status groups. All within-host GII.4 viral populations showed amino acid changes at blocking epitopes over time, and the majority of VP1 amino acid mutations were located at the capsid surface.<bold>Conclusions: </bold>This study found viruses in immunocompromised hosts that are genetically distinct from viruses circulating in the general population, and these patients therefore may contain a reservoir for newly emerging strains. Future studies need to determine whether these new strains are of risk to other immunocompromised patients and the general population.
- Subjects
NOROVIRUSES; NUCLEOTIDE sequencing; NOROVIRUS diseases; GASTROENTERITIS; VIRAL evolution; HOSTS (Biology); CHRONIC diseases; COMPARATIVE studies; BIOLOGICAL evolution; FECES; GENOMES; RESEARCH methodology; MEDICAL cooperation; PUBLIC health; RESEARCH; RNA; RNA viruses; TIME; VIRAL physiology; EVALUATION research; RETROSPECTIVE studies; IMMUNOCOMPROMISED patients; SEQUENCE analysis
- Publication
Journal of Infectious Diseases, 2017, Vol 216, Issue 12, p1513
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jix520