Genetic Analysis of Reemerging GII.P16-GII.2 Noroviruses in 2016-2017 in China

During 2016-2017, the previously rare GII.P16-GII.2 norovirus suddenly emerged as the predominant genotype causing gastroenteritis outbreaks in China and other countries. Its origin, phylodynamics, and mechanism behind the predominance remain unclear. Bayesian phylogenetic analyses were performed on 180 full capsid and 150 polymerase sequences of 2016-2017 GII.P16-GII.2 noroviruses in China, and those for all publicly available GII.P16 and GII.2 sequences. Saliva-based histo-blood group antigen (HBGA) binding assays and crystal structural analysis were conducted by using the P proteins of 2016-2017 GII.P16-GII.2 noroviruses. The reemerging GII.P16-GII.2 norovirus showed a rapid genetic diversification after its emergence in 2012-2013. The antigenicity and HBGA binding profile of the early 2016-2017 and pre-2016 GII.2 noroviruses were similar. A further variant with a single Val256Ile mutation and the conventionally orientated Asp382 in the VP1 protein showed an expanded HBGA-binding spectrum. Mutations on the surface of polymerase that could alter its function were seen, which may help to accelerate the VP1 gene evolution to 5.5 × 10-3 substitutions per site per year. This virus can be traced back to Pearl River Delta, China. Our findings provide new insights into GII.2 norovirus epidemics and highlight the necessity of enhanced global surveillance for potential epidemics of rare-genotype noroviruses.