Global and regional circulation trends of norovirus genotypes and recombinants, 1995–2019: A comprehensive review of sequences from public databases

Abstract

Human noroviruses are the leading global cause of viral gastroenteritis. Attempts at developing effective vaccines and treatments against norovirus disease have been stymied by the extreme genetic diversity and rapid geographic distribution of these viruses. The emergence and replacement of predominantly circulating norovirus genotypes has primarily been attributed to mutations on the VP1 capsid protein leading to genetic drift, and more recently to recombination events between the ORF1/ORF2 junction. However, large-scale research into the historical and geographic distribution of recombinant norovirus strains has been limited in the literature. We performed a comprehensive historical analysis on 30,810 human norovirus sequences submitted to public databases between the years 1995 and 2019. During this time, 37 capsid genotypes and 56 polymerase types were detected across 90 different countries, and 97 unique recombinant genomes were also identified. GII.4, both capsid and polymerase, was the predominately circulating type worldwide for the majority of this time span, save for a brief swell of GII.17 and GII.2 capsid genotypes and a near-total eclipse by GII.P16, GII.P21 and GII.P31 beginning in 2013. Interestingly, an analysis of 4067 recombinants found that 50.2% (N = 2039) of all recorded sequences belonged to three recently emerged recombinant strains: GII.2[P16], GII.4[P31], and GII.4[P16]. This analysis should provide an important historical foundation for future studies that evaluate the emergence and distribution of noroviruses, as well as the design of cross-protective vaccines. | INTRODUCTIONAcute gastroenteritis is a major cause of morbidity and mortality worldwide, particularly in infants and young children from developing countries. Following the successful implementation of rotavirus vaccines, noroviruses have become the most important cause of viral gastroenteritis in the US and other developed countries. 1 Norovirus disease is spread by contact with contaminated food or infected individuals, with intense symptoms of nausea, diarrhoea and abdominal pain that arise 12-48 h after initial infection. It is estimated that noroviruses annually cause up to 200,000 deaths and approximately $60 billion in financial burdens associated with health care and productivity loss worldwide. 2,3

Norovirus outbreaks in China, 2000–2018: A systematic review

“…These data indicate that GII.4 2006b, GII.4 Sydney 2012, GII.17, and GII.2 [P16] emerged and became predominant in China in 2006–2007, 2012–2013, 2014–2015, and 2016–2017, respectively. In accordance with a recent study that performed an analysis on 30,810 human norovirus sequences submitted during 1995–2019 at global level, GII.4 was the predominately circulating type worldwide, GII.17 and GII.2 capsid genotypes had a brief prevalence in 2014 and 2017 48 . The emergence of new variants often leads to an increase in norovirus outbreaks, and the changes in the predominant genotype correspond to the increases in norovirus outbreaks in 2006–2007, 2012–2013, 2014–2015, and 2017.…”

Norovirus and rotavirus susceptibility : studies from a Nicaraguan birth cohort

“…Genotype GII.4 accounts for more than 50% of the norovirus episodes worldwide (52). This genotype is further divided into specific variants based on phylogenetic clustering and after they become epidemic in at least two geographically diverse locations (53).…”

The emergence of recombinant norovirus GII.12[P16] and predominance of GII.3[P12] strains in pediatric patients with acute gastroenteritis in Thailand, 2019–2020

“…NoV GII.P4 is the most predominant P‐type. However, the emergence of other P‐types such as GII.P16, GII.P17, and GII.P31 have been documented and recently became the most common P‐types during 2013‐2019 7 …”

“…6 Among these, 37 genotypes of NoV detected in the human population have been reported worldwide. 7 NoV GII.4 predominate continuously over 2 decades with six major pandemic variants have been identified. 8 On the basis of partial RNAdependent RNA-polymerase (RdRp) nucleotide (nt) sequences, NoV is divided into eight polymerase (P) groups (GI.P-GVII.P and GX.P).…”

“…However, the emergence of other P-types such as GII.P16, GII.P17, and GII.P31 have been documented and recently became the most common P-types during 2013-2019. 7 Since the recombination event of NoV has been increasingly reported worldwide, dual-typing (genotype and P-type) is recently proposed for the nomenclature of NoV strain. So far, more than 30 recombinant patterns have been reported from 2015 to 2020.…”