Abstract
Noroviruses evolve by antigenic drift and recombination, which occurs most frequently at the junction between the non-structural and structural protein coding genomic regions. In 2015, a novel GII.P16-GII.4 Sydney recombinant strain emerged, replacing the predominance of GII.Pe-GII.4 Sydney among US outbreaks. Distinct from GII.P16 polymerases detected since 2010, this novel GII.P16 was subsequently detected among GII.1, GII.2, GII.3, GII.10 and GII.12 viruses, prompting an investigation on the unique characteristics of these viruses. Norovirus positive samples (n = 1807) were dual-typed, of which a subset (n = 124) was sequenced to yield near-complete genomes. CaliciNet and National Outbreak Reporting System (NORS) records were matched to link outbreak characteristics and case outcomes to molecular data and GenBank was mined for contextualization. Recombination with the novel GII.P16 polymerase extended GII.4 Sydney predominance and increased the number of GII.2 outbreaks in the US. Introduction of the novel GII.P16 noroviruses occurred without unique amino acid changes in VP1, more severe case outcomes, or differences in affected population. However, unique changes were found among NS1/2, NS4 and VP2 proteins, which have immune antagonistic functions, and the RdRp. Multiple polymerase-capsid combinations were detected among GII viruses including 11 involving GII.P16. Molecular surveillance of protein sequences from norovirus genomes can inform the functional importance of amino acid changes in emerging recombinant viruses and aid in vaccine and antiviral formulation.
Highlights
Noroviruses are a major cause of sporadic and epidemic acute gastrointestinal illness worldwide [1,2,3]
Of the 4,123 norovirus outbreaks submitted to CaliciNet between September 2013 and August
We report the emergence of a novel GII.P16 polymerase that is associated with multiple capsid types
Summary
Noroviruses are a major cause of sporadic and epidemic acute gastrointestinal illness worldwide [1,2,3]. Norovirus affects people of all ages, and most healthy individuals resolve symptoms within 48–72 h, whereas immunocompromised, very young, and elderly individuals have a higher likelihood of more protracted or severe outcomes [5,6]. Norovirus is a non-enveloped positive-sense single-stranded RNA virus of approximately 7.5 kb in length within the family Caliciviridae. ORF1 encodes a large polyprotein that is cleaved into six nonstructural proteins (NS1/2, NS3, NS4, NS5, NS6, and NS7). ORF2 and ORF3 encode major (VP1) and minor (VP2) capsid proteins, respectively [6]. Based on VP1, noroviruses are classified into at least seven genogroups (GI to GVII), which can be further divided into at least
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