2019
DOI: 10.1101/668772
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Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains

Abstract: (max 250) 14Word count in Importance: 110 (max 150) 15 Word count in Main Text: 5698 16Abstract 25 26 GII.4 noroviruses are a major cause of acute gastroenteritis. Their dominance has been partially 27 explained by the continuous emergence of antigenically distinct variants. To gain insights on the 28 mechanisms of viral emergence and population dynamics of GII.4 noroviruses, we performed 29 large-scale genomics, structural, and mutational analyses of the viral capsid protein (VP1). GII.4 30 noroviruses exhibi… Show more

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Cited by 2 publications
(6 citation statements)
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“…Thus, antigenic site A consists of residues 294-298, 368, 372, 373; antigenic site C of 339-341, 375-378; antigenic site D of 393-397; antigenic site E of 407, 411-414; and antigenic site G of 352, 355-357, 359, 364 (Figure 1, panel D). [66][67][68][69][70] Most of these sites are on the loops and/or outer surface of the P2 subdomain where they can interact with neutralizing antibodies and attachment factors. Notably, although the overall structure of the capsid is mostly conserved between the different variants of GII.4, the length varies among genotypes.…”
Section: The Impact Of Norovirus Diversity On Immunitymentioning
confidence: 99%
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“…Thus, antigenic site A consists of residues 294-298, 368, 372, 373; antigenic site C of 339-341, 375-378; antigenic site D of 393-397; antigenic site E of 407, 411-414; and antigenic site G of 352, 355-357, 359, 364 (Figure 1, panel D). [66][67][68][69][70] Most of these sites are on the loops and/or outer surface of the P2 subdomain where they can interact with neutralizing antibodies and attachment factors. Notably, although the overall structure of the capsid is mostly conserved between the different variants of GII.4, the length varies among genotypes.…”
Section: The Impact Of Norovirus Diversity On Immunitymentioning
confidence: 99%
“…Changes on these antigenic sites, particularly antigenic sites A, C, and G, also correlate with the circulation patterns of GII.4 variants (Figure 1, panel E, right). 70 Notably, while mutations in single antigenic sites can abolish mAbs binding, 69,70 largescale antigenic studies suggest that multiple sites are required for antigenic diversification of GII.4. 38 Indeed, structural analyses identified mAbs with footprint spanning multiple antigenic sites, suggesting that the virus may need to change multiple sites to evade the host immune response.…”
Section: The Impact Of Norovirus Diversity On Immunitymentioning
confidence: 99%
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“…The novel GII.4 variant has emerged every 2-5 years and presented amino acid changes in five antigenic sites (7) associated with viral escape from herd immunity (8,9). This epochal evolution pattern is regarded as the principal mechanism adopted by GII.4 to sustain its predominance and has led to successive pandemics in the global population (10)(11)(12).…”
Section: Introductionmentioning
confidence: 99%