Higher Viral Load of Emerging Norovirus GII.P16-GII.2 than Pandemic GII.4 and Epidemic GII.17, Hong Kong, China

Cheung, Sarah K.C.; Kwok, Ka‐li; Zhang, Lin-Yao; Mohammad, Kirran N.; Lui, Grace; Lee, Nelson; Nelson, E. Anthony S.; Lai, Robin Kit-Ho; Leung, Ting Fan; Chan, Paul K.S.; Chan, Martin C.W.

doi:10.3201/eid2501.180395

Cited by 35 publications

(25 citation statements)

References 15 publications

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“…The contribution of the RdRp to the evolutionary rate of caliciviruses became even more clear with the recent success of recombinant GII.2 and GII.4 viruses that acquired a new polymerase variant. For example, the reemerged recombinant norovirus GII.P16-GII.2 that differs from previous GII.P16-GII.2 strains by 5 amino acids in the RdRp (Ruis et al, 2017), results in high virus loads in feces, possesses a relatively high evolutionary rate (5.5 × 10 -3 substitutions/site/year), and has rapidly spread across the world (Ao et al, 2018; Cheung et al, 2019). It has been suggested that the amino acid changes in the new RdRp affect the kinetic properties and the fidelity of the enzyme, but the exact mechanistic details remain unknown.…”

Section: Enzymatic Properties Of Calicivirus Rdrpsmentioning

confidence: 99%

Calicivirus RNA-Dependent RNA Polymerases: Evolution, Structure, Protein Dynamics, and Function

et al. 2019

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The Caliciviridae are viruses with a positive-sense, single-stranded RNA genome that is packaged into an icosahedral, environmentally stable protein capsid. The family contains five genera ( Norovirus , Nebovirus, Sapovirus , Lagovirus , and Vesivirus ) that infect vertebrates including amphibians, reptiles, birds, and mammals. The RNA-dependent RNA polymerase (RdRp) replicates the genome of RNA viruses and can speed up evolution due to its error-prone nature. Studying calicivirus RdRps in the context of genuine virus replication is often hampered by a lack of suitable model systems. Enteric caliciviruses and RHDV in particular are notoriously difficult to propagate in cell culture; therefore, molecular studies of replication mechanisms are challenging. Nevertheless, research on recombinant proteins has revealed several unexpected characteristics of calicivirus RdRps. For example, the RdRps of RHDV and related lagoviruses possess the ability to expose a hydrophobic motif, to rearrange Golgi membranes, and to copy RNA at unusually high temperatures. This review is focused on the structural dynamics, biochemical properties, kinetics, and putative interaction partners of these RdRps. In addition, we discuss the possible existence of a conserved but as yet undescribed structural element that is shared amongst the RdRps of all caliciviruses.

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Section: Enzymatic Properties Of Calicivirus Rdrpsmentioning

confidence: 99%

Calicivirus RNA-Dependent RNA Polymerases: Evolution, Structure, Protein Dynamics, and Function

et al. 2019

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“…Additionally, the increase in norovirus activity at the end of 2016 to 2017 may have occurred because of the emergent GII.P16/GII.2 recombinant ( Fu et al, 2017 ; Kwok et al, 2017 ; Liu et al, 2017 ). This GII.P16 genotype presented several amino acid changes in non-structural proteins, such as RdRp, and these changed seemed to facilitate its transmission ( Cannon et al, 2017 ; Tohma et al, 2017 ; Cheung et al, 2019 ). In this study, we analyzed the complete genomes of GII.4 strains collected over 5 years to understand their genetic characteristics and investigate the emergence of GII.P16/GII.4.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and Molecular Analysis of Complete Genome Sequences of Norovirus From Brazil: Emerging Recombinant Strain GII.P16/GII.4

et al. 2020

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Noroviruses (NoVs) are enteric viruses that cause acute gastroenteritis, and the pandemic GII.4 genotype is spreading and evolving rapidly. The recombinant GII.P16/GII.4_Sydney strain emerged in 2016, replacing GII.P31/GII.4_Sydney (GII.P31 formerly known as GII.Pe) in some countries. We analyzed the complete genome of 20 NoV strains (17 GII.P31/GII.4_ Sydney and 3 GII.P16/GII.4_Sydney) from Belém and Manaus, Brazil, collected from 2012 to 2016. Phylogenetic trees were constructed by maximum likelihood method from 191 full NoV-VP1 sequences, demonstrated segregation of the Sydney lineage in two larger clades, suggesting that GII.4 strains associated with GII.P16 already have modifications compared with GII.P31/GII.4. Additionally, the Bayesian Markov Chain Monte Carlo method was used to reconstruct a time-scaled phylogenetic tree formed by GII.P16 ORF1 sequences (n = 117) and three complete GII.P16 sequences from Belém. The phylogenetic tree indicated the presence of six clades classified into different capsid genotypes and locations. Evolutionary rates of the ORF1 gene of GII.P16 strains was estimated at 2.01 × 10 −3 substitutions/site/year, and the most recent common ancestors were estimated in 2011 (2011-2012, 95% HPD). Comparing the amino acid (AA) sequence coding for ORF1 with the prototype strain GII.P16/GII.4, 36 AA changes were observed, mainly in the non-structural proteins p48, p22, and RdRp. GII.P16/GII.4 strains of this study presented changes in amino acids 310, 333, 373, and 393 of the antigenic sites in the P2 subdomain, and ML tree indicating the division within the Sydney lineage according to the GII.P16 and GII.P31 polymerases. Notably, as noroviruses have high recombination rates and the GII.4 genotype was prevalent for a long time in several locations, additional and continuous evolutionary analyses of this new genotype should be needed in the future.

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“…For example, the pandemic GII.P16/GII.4 Sydney 2012 norovirus, which does not contain unique substitutions in the capsid, has substitutions within the RdRp that are proposed to increase transmissibility [69]. Infection with this variant also resulted in increased viral shedding compared to other norovirus genotypes, as measured by higher faecal viral loads [70]. Previous studies have shown that RdRp fidelity and intra-host viral diversity affect transmissibility of murine norovirus in vivo , with high-fidelity variants being less efficiently transmitted than the wild-type variant [71].…”

Section: Discussionmentioning

confidence: 99%

Frequent intergenotypic recombination between the non-structural and structural genes is a major driver of epidemiological fitness in caliciviruses

Mahar

Jenckel

Huang

et al. 2021

Preprint

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The diversity of lagoviruses (Caliciviridae) in Australia has increased considerably. By the end of 2017, five variants from three viral genotypes were present in populations of Australian rabbits, while prior to 2014 only two variants were known. To understand the interactions between these lagovirus variants we monitored their geographical distribution and relative incidence over time through a landscape-scale competition study, and from this, revealed potential drivers of epidemiological fitness. Within three years of the arrival of GI.1bP-GI.2 (RHDV2) into Australia, we observed the emergence of two novel recombinant lagovirus variants, GI.4eP-GI.2 (4e-recombinant) in New South Wales and GI.4cP-GI.2 (4c-recombinant) in Victoria. Although both novel recombinants contain the non-structural genes from benign, rabbit-specific, enterotropic viruses, these variants were recovered from the livers of both rabbits and hares that had died acutely. This suggests that determinants of host and tissue tropism for lagoviruses are associated with the structural genes, and that tropism is intricately connected with pathogenicity. Phylogenetic analyses demonstrated that the 4c-recombinant emerged independently on multiple occasions, with five distinct lineages observed. Both new recombinant variants replaced the previous dominant parental RHDV2 in their respective geographical areas, despite sharing an identical or near-identical (i.e., single amino acid change) major capsid protein with the parental virus. This suggests that epidemiological fitness of these recombinants was not driven by antigenic variation in the capsid, implicating the non-structural genes as key drivers of epidemiological fitness. Molecular clock estimates place the GI4.e recombination event in early to mid-2015, while the five GI.4c recombination events occurred from late 2015 through to early 2017. The emergence of at least six viable recombinant variants within a two-year period highlights an unprecedented frequency of these events, detectable only due to intensive surveillance, and demonstrates the importance of recombination in lagovirus evolution.

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Higher Viral Load of Emerging Norovirus GII.P16-GII.2 than Pandemic GII.4 and Epidemic GII.17, Hong Kong, China

Cited by 35 publications

References 15 publications

Calicivirus RNA-Dependent RNA Polymerases: Evolution, Structure, Protein Dynamics, and Function

Calicivirus RNA-Dependent RNA Polymerases: Evolution, Structure, Protein Dynamics, and Function

Evolutionary and Molecular Analysis of Complete Genome Sequences of Norovirus From Brazil: Emerging Recombinant Strain GII.P16/GII.4

Frequent intergenotypic recombination between the non-structural and structural genes is a major driver of epidemiological fitness in caliciviruses

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