Contribution of intra- and interhost dynamics to norovirus evolution.
Norovirus (NoV) is an emerging RNA virus that has been associated with global epidemics of gastroenteritis. Each global epidemic arises with the emergence of novel antigenic variants. While the majority of NoV infections are mild and self-limiting, in the young, elderly, and immunocompromised, severe and prolonged illness can result. As yet, there is no vaccine or therapeutic treatment to prevent or control infection. In order to design effective control strategies, it is important to understand the mechanisms and source of the new antigenic variants. In this study, we used next-generation sequencing (NGS) technology to investigate genetic diversification in three contexts: the impact of a NoV transmission event on viral diversity and the contribution to diversity of intrahost evolution over both a short period of time (10 days), in accordance with a typical acute NoV infection, and a prolonged period of time (288 days), as observed for NoV chronic infections of immunocompromised individuals. Investigations of the transmission event revealed that minor variants at frequencies as low as 0.01% were successfully transmitted, indicating that transmission is an important source of diversity at the interhost level of NoV evolution. Our results also suggest that chronically infected immunocompromised subjects represent a potential reservoir for the emergence of new viral variants. In contrast, in a typical acute NoV infection, the viral population was highly homogenous and relatively stable. These results indicate that the evolution of NoV occurs through multiple mechanisms.
School of Biotechnology and Biomolecular Sciences, Faculty of Science,a and School of Medical Sciences, Faculty of Medicine,b University of New South Wales, Sydney,Australia.
Rowena A
RA
Bull
John-Sebastian
JS
Eden
Fabio
F
Luciani
Kerensa
K
McElroy
William D
WD
Rawlinson
Peter A
PA
White
D017250:Caliciviridae Infections / Q000635:transmission / Q000821:virology*; D002648:Child; D015331:Cohort Studies; D019143:Evolution, Molecular; D005260:Female; D005759:Gastroenteritis / Q000821:virology*; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D029322:Norovirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny