Early evolution and transmission of GII.P16-GII.2 norovirus in China

Norovirus is the most common cause of acute gastroenteritis worldwide. During 2016-2017, a novel recombinant GII.P16-GII.2 genotype of norovirus suddenly appeared and over the next several years became the predominant strain in both China and worldwide. To better understand the origin and diffusion of the GII.P16-GII.2 genotype in China, we conducted molecular evolutionary analyses, including phylodynamics and phylogeography. Moreover, to trace person-to-person transmission of GII.P16-GII.2 norovirus, we applied the novel method, TransPhylo, to a historical phylogeny using sequences obtained from a publicly available database. A time-scaled phylogenetic tree indicated that the time to the most recent common ancestor of the GII.P16-GII.2 major capsid protein (VP1) gene diverged from the GII.P2-GII.2 VP1 gene at 2,001.03 with an evolutionary rate of 3.32 × 10-3 substitutions/site/year. The time to the most recent common ancestor of the GII.P16-GII.2 RNA-dependent RNA polymerase region diverged from the GII.P16-GII.4 RNA-dependent RNA polymerase region at 2,013.28 with an evolutionary rate of 9.44 × 10-3 substitutions/site/year. Of these 2 genomic regions, VP1 gene sequence variations were the most influenced by selective pressure. A phylogeographic analysis showed that GII.P16-GII.2 strains in China communicated most frequently with those in the United States, Australia, Thailand, and Russia, suggesting import from Australia to Taiwan and from the United States to Guangdong. TransPhylo analyses indicated that the basic reproductive number (R0) and sampling proportion (pi) of GII.P16-GII.2 norovirus were 1.99 (95% confidence interval: 1.58-2.44) and 0.76 (95% confidence interval: 0.63-0.88), respectively. Strains from the United States and Australia were responsible for large spread during the evolution and transmission of the virus. Coastal cities and places with high population densities should be closely monitored for norovirus.