Human norovirus hyper-mutation revealed by ultra-deep sequencing
Por:
Cuevas JM, Combe M, Torres-Puente M, Garijo R, Guix S, Buesa J, Rodriguez-Diaz J and Sanjuan R
Publicada:
1 jul 2016
Resumen:
Human noroviruses (NoVs) are a major cause of gastroenteritis worldwide.
It is thought that, similar to other RNA viruses, high mutation rates
allow NoVs to evolve fast and to undergo rapid immune escape at the
population level. However, the rate and spectrum of spontaneous
mutations of human NoVs have not been quantified previously. Here, we
analyzed the intra-patient diversity of the NoV capsid by carrying out
RT-PCR and ultra-deep sequencing with 100,000-fold coverage of 16 stool
samples from symptomatic patients. This revealed the presence of
low-frequency sequences carrying large numbers of U-to-C or A-to-G base
transitions, suggesting a role for hyper-mutation in NoV diversity. To
more directly test for hyper-mutation, we performed transfection assays
in which the production of mutations was restricted to a single cell
infection cycle. This confirmed the presence of sequences with multiple
U-to-C/A-to-G transitions, and suggested that hyper-mutation contributed
a large fraction of the total NoV spontaneous mutation rate. The type of
changes produced and their sequence context are compatible with
ADAR-mediated editing of the viral RNA. (C) 2016 Elsevier B.V. All
rights reserved.
Filiaciones:
Cuevas JM:
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Valencia, Spain
Combe M:
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Valencia, Spain
:
Fundacion para el Fomento de la Investigacion Sanitaria y Biomedica de la Comunitat Valenciana, Valencia, Spain
Garijo R:
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Valencia, Spain
Guix S:
Departament de Microbiologia, Universitat de Barcelona, Barcelona, Spain
Buesa J:
Departament de Microbiologia, Universitat de Valencia, Valencia, Spain
Rodriguez-Diaz J:
Departament de Microbiologia, Universitat de Valencia, Valencia, Spain
Sanjuan R:
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Valencia, Spain
Departament de Genetica, Universitat de Valencia, Valencia, Spain
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