Re-emergence of a GII.4 Norovirus Sydney 2012 Variant Equipped with GII.P16 RdRp and Its Predominance over Novel Variants of GII.17 in South Korea in 2016

Abstract

Noroviruses are major causative pathogen of nonbacterial acute gastroenteritis worldwide. Of the seven genogroups of noroviruses suggested recently, genogroup II genotype 4 (GII.4) had been the most common genotype identified in hospitalized patients in the last few decades. However, since the latter half of 2014, new variants of GII.17 have been reported as the main causes of outbreaks over GII.4 in East Asia and have also occurred in America and Europe. In this study, we monitored norovirus GII in coastal streams at South Gyeongsang province and South Jeolla province of South Korea from March 2015 to May 2016. Norovirus GII.17 capsid sequences were predominantly detected until September 2015 in water samples. However, we found that the number of positive cases of the norovirus GII.4 Sydney 2012 capsid sequence has been increasing since December 2015, overtaking that of GII.17 in 2016. The RdRp genotype of this predominant GII.4 variant in 2016 was identified as GII.P16. The emergence and predominance of the GII.4 pandemic capsid sequence harboring a different RdRp genotype suggested the potential for a future pandemic.

Genetic and Epidemiologic Trends of Norovirus Outbreaks in the United States from 2013 to 2016 Demonstrated Emergence of Novel GII.4 Recombinant Viruses

“…Interestingly, the GII.P16 sequences shared by GII.2 and GII.4 Sydney genotypes were nearly identical to the GII.P16-GII.4 Sydney sequences reported in Japan in January of 2016 (29) and in coastal waters impacted by sewage in China (44). GII.2, GII.3, GII.10, GII.12, GII.13, and GII.17 viruses are known to harbor GII.P16 polymerases.…”

The emerging GII.P16-GII.4 Sydney 2012 norovirus lineage is circulating worldwide, arose by late-2014 and contains polymerase changes that may increase virus transmission

“…Here, we demonstrate that the emerging GII.P16-GII.4 Sydney 2012 norovirus lineage is circulating in the UK and USA, in addition to previous reports of circulation in Asia and Germany [6–8]. Analysis of available sequences suggests that this lineage has been circulating since October 2014 or earlier (Fig 2).…”

“…While the first five pandemic strains contained the GII.P4 RdRp, the most recent pandemic strain (Sydney 2012) circulated more commonly with the GII.Pe RdRp. Recent reports demonstrated circulation of the Sydney 2012 capsid with a GII.P16 RdRp in South Korea, Japan and Germany [6–8]. While the GII.P16 RdRp is not typically highly prevalent, a GII.P16-GII.2 virus was the dominant strain amongst a large peak of norovirus infections in Germany in Winter 2016 [8].…”

Phylogenetic Analyses Suggest that Factors Other Than the Capsid Protein Play a Role in the Epidemic Potential of GII.2 Norovirus

“…This seems contradictory; however, the predominance of GII.P16-GII.2 viruses in certain countries (20, 21) coincided with the detection of a novel GII.4 strain, GII.P16-GII.4_Sydney (20, 42–44), suggesting that this GII.P16 polymerase could have a positive impact on the fitness of the virus. Indeed, using the murine norovirus model, Arias et al have shown that the fidelity of the polymerase could influence the transmissibility of the virus (45).…”