Epidemiological and evolutionary dynamics and spatio-temporal transmission of re-emerging epidemic GII.2 noroviruses

M.Phil. ; Norovirus is the leading cause of acute gastroenteritis and is causing a high disease burden globally in consequence of lacking antivirals and vaccine for treating and preventing norovirus infections. Development of norovirus vaccine has been hindered by the broad genetic diversity of norovirus, the highly dynamic virus genotype distribution in different age groups and settings, and the co-circulation of pandemic genogroup II genotype 4 (GII.4) and epidemic non-GII.4 noroviruses. Close monitoring of circulating noroviruses and identification of epicenter for establishing focused surveillance is warranted to guide disease control and vaccine development. ; A routine molecular surveillance of noroviruses was implemented during July 2016 - December 2017 in our hospitals in Hong Kong, China. Altogether, seven hundred and fifteen samples were collected from 687 case-patients. An increased detection of a previously uncommon norovirus recombinant, GII.P16-GII.2 was observed in our surveillance from 2.7% in August 2016 to 64.8% in February 2017. This GII.P16-GII.2 was also detected in other major cities of China, Germany and Japan, indicating this variant was geographically widespread. Of note, an age shift from young children aged under 5 years towards older children and young adults and 21 case-patients 18-40 years of age, an immunocompetent age group rarely seen in severe norovirus infections, was observed in our hospital cohort, suggesting this new norovirus might be an immune-escaped variant or might have higher virulence. These findings highlight the need to closely monitor this re-emerging recombinant GII.P16-GII.2. ; A subset of GII.P16-GII.2 strains (n=93) was hence selected for full-lengthviral protein 1 (VP1) sequencing. Phylogenetic analysis was performed on a dataset containing GII.P16-GII.2 VP1 sequences from our surveillance and GenBank (n=535). By tree topology, ancestral strains forming the bottom of this re-emerging GII.2 cluster were from Hong Kong and southern China. Earliest strains ...