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

Ruis, Christopher; Roy, Sunando; Brown, Julianne R.; Allen, David J.; Goldstein, Richard A.; Breuer, Judith

doi:10.1371/journal.pone.0179572

Cited by 68 publications

(80 citation statements)

References 15 publications

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“…GII.4 HuNoVs have caused pandemics and are now the major circulating strains [9][10][11]. Currently, a recombinant GII.4 Sydney pandemic strain (GII.P16-GII.4 Sydney) causes the majority of infections, making it the most suitable strain for vaccine development [12,13].…”

Section: Introductionmentioning

confidence: 99%

Vero Cells as a Mammalian Cell Substrate for Human Norovirus

Todd

Tripp

2020

Viruses

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Human norovirus (HuNoV) is a principal cause of acute gastroenteritis worldwide, particularly in developing countries. Its global prevalence is underscored by more serious morbidity and some mortality in the young (<5 years) and the elderly. To date, there are no licensed vaccines or approved therapeutics for HuNoV, mostly because there are limited cell culture systems and small animal models available. Recently described cell culture systems are not ideal substrates for HuNoV vaccine development because they are not clonal or only support a single strain. In this study, we show Vero cell-based replication of two pandemic GII.4 HuNoV strains and one GII.3 strain and confirm exosome-mediated HuNoV infection in Vero cells. Lastly, we show that trypsin addition to virus cultures or disruption of Vero cell host genes can modestly increase HuNoV replication. These data provide support for Vero cells as a cell culture model for HuNoV.

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Section: Introductionmentioning

confidence: 99%

Vero Cells as a Mammalian Cell Substrate for Human Norovirus

Todd

Tripp

2020

Viruses

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“…We next examined the potential influence of other genomic regions on the pandemic emergence of Sydney 2012. It is unlikely that the nonstructural polyprotein drove Sydney 2012 pandemic spread, as this variant co-circulated with the nonstructural polyprotein from the unrelated GII.Pe, GII.P4 and (more recently) GII.P16 genotypes (Figure S6) (Wong et al 2013; Ruis et al 2017). Substitutions occurred within VP2 leading to (site 148) and (sites 158, 205) and remained highly conserved within the Sydney 2012 clade (Figures 3E, S5).…”

Section: Resultsmentioning

confidence: 99%

Preadaptation of pandemic GII.4 noroviruses in hidden virus reservoirs years before emergence

Ruis

Lindesmith²,

Mallory³

et al. 2019

Preprint

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39The control of pandemic pathogens depends on early prediction of pandemic variants and, more generally, 40 understanding origins of such variants and factors that drive their global spread. This is especially 41 important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of 42 millions of annual gastroenteritis cases. Previous studies have suggested that new GII.4 pandemic viruses 43 evolve from previous pandemic variants through substitutions in the antigenic region of the VP1 protein 44 that enable evasion of host population immunity, leading to global spread. In contrast, we show here that 45 the acquisition of new genetic and antigenic characteristics is not the proximal driver of new pandemics. 46 Instead, pandemic GII.4 viruses circulate undetected for years before causing a new pandemic, during 47 which time they diversify and spread over wide geographical areas. Serological data demonstrate that by 48 2003, some nine years before it emerged as a new pandemic, the ancestral 2012 pandemic strain had 49 already acquired the antigenic characteristics that allowed it to evade prevailing population immunity 50 against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic 51 changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes 52 in host population immunity that enable pandemic spread of an antigenically-preadapted GII.4 variant. 53 These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently 54 unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent 55 future pandemics. 56 57 Significance 58 Norovirus pandemics and their associated public health and economic costs could be prevented by 59 effective vaccines. However, vaccine development and distribution will require identification of the 60 sources and drivers of new pandemics. We here use phylogenetics and serological experiments to develop 61 and test a new hypothesis of pandemic norovirus emergence. We find that pandemic noroviruses pre-62 adapt, diversify and spread worldwide years prior to emergence, strongly indicating that genetic changes 63 are necessary but not sufficient to drive a new pandemic. We instead suggest that changes in population 64 immunity enable pandemic emergence of a pre-adapted low-level variant. These findings indicate that 65 prediction of new pandemics will require surveillance of under-sampled virus reservoirs and that 66 norovirus vaccines will need to elicit broad immunity. 67 68 Parra et al. 2017), as well as other geographically-limited outbreaks caused by epidemic variants 78 (Siebenga et al. 2009; Eden et al. 2014). 79 80 Vaccines currently under development offer promise to mitigate the global economic and health impact 81 of new GII.4 pandemics (Lindesmith et al. 2015). However, effective vaccine design and distribution 82 depend on understanding the sources from which new pandemic var...

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“…In Brazil, a great diversity of norovirus GII.4 variants, as well as intra-genotype recombinant strains, have circulated throughout the country, following the global pattern observed in many studies [ 28 , 29 , 30 ]. Herein, we described the detection in Brazil of an emergent recombinant genotype that is currently circulating in many countries worldwide [ 15 , 16 , 17 , 18 , 19 ]. During the study period, we observed a change in the circulation pattern of the recombinant strains, with GII.Pe-GII.4 Sydney 2012 predominant in 2015, followed by an emergence and predominance of GII.P16-GII.4 Sydney in 2016.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, GII.P16-GII.4 has been reported in sporadic cases and outbreaks from September to December 2016 in Germany and in increased outbreaks during 2016/2017 in France, and it was detected in the waters of coastal streams in South Korea in December 2015, replacing the formerly dominant strain GII.P17-GII.17 [ 17 , 18 ]. The last report came from sporadic cases and outbreaks during 2015–2016 in England [ 19 ]. Our study documents for the first time the emergence of this strain in samples from children with AGE on the southeastern coast of Brazil.…”

Section: Introductionmentioning

confidence: 99%

Detection and molecular characterization of the novel recombinant norovirus GII.P16-GII.4 Sydney in southeastern Brazil in 2016

et al. 2017

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Noroviruses are the leading cause of acute gastroenteritis (AGE) in all age groups worldwide. Despite the high genetic diversity of noroviruses, most AGE outbreaks are caused by a single norovirus genotype: GII.4. Since 1995, several different variants of norovirus GII.4 have been associated with pandemics, with each variant circulating for 3 to 8 years. The Sydney_2012 variant was first reported in Australia and then in other countries. A new variant, GII.P16-GII.4, was recently described in Japan and South Korea and then in the USA, France, Germany and England. In our study, 190 faecal specimens were collected from children admitted to a paediatric hospital and a public health facility during a surveillance study of sporadic cases of AGE conducted between January 2015 and July 2016. The norovirus was detected by RT-qPCR in 51 samples (26.8%), and in 37 of them (72.5%), the ORF1-2 junction was successfully sequenced. The new recombinant GII.P16-GII.4 Sydney was revealed for the first time in Brazil in 2016 and predominated among other strains (9 GII.Pe-GII.4, 3 GII.P17-GII.17, 1 GII.Pg-GII.1, 1 GII.P16-GII.3 and 1 GII.PNA-GII.4). The epidemiological significance of this new recombinant is still unknown, but continuous surveillance studies may evaluate its impact on the population, its potential to replace the first recombinant GII.Pe-GII.4 Sydney 2012 variant, and the emergence of new recombinant forms of GII.P16.

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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

Cited by 68 publications

References 15 publications

Vero Cells as a Mammalian Cell Substrate for Human Norovirus

Vero Cells as a Mammalian Cell Substrate for Human Norovirus

Preadaptation of pandemic GII.4 noroviruses in hidden virus reservoirs years before emergence

Detection and molecular characterization of the novel recombinant norovirus GII.P16-GII.4 Sydney in southeastern Brazil in 2016

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