Emergence of Novel Norovirus GII.4 Variant

Abstract

We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017-2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development.

Keywords: South Africa; United Kingdom; United States; acute gastroenteritis; enteric infections; norovirus; viruses.

Figure 1

Phylogenetic trees of the emerging novel norovirus GII.4 strains on 3 continents. A) Common genotyping region C; 250 nt from the 5′ end of ORF2; B) complete VP1 aa sequences. Phylogenetic trees show novel GII.4 San Francisco strains and GII.4 variants, including recently identified clusters like GII.4 Hong Kong. Evolutionary analyses were conducted in MEGA X (https://www.megasoftware.net) using the maximum-likelihood method based on the Tamura-Nei model for the C region and Jones-Taylor-Thornton matrix-based model for VP1. We used a discrete gamma distribution to model evolutionary rate differences among sites; 5 categories γ parameter = 0.2174. Bootstrap (100) values are indicated at the nodes. Trees were drawn to scale. Scale bar represents nucleotide substitutions per site. ORF, open reading frame; VP1, viral protein 1.

Figure 2

Structural changes of emergent novel norovirus GII.4 strains from 3 continents. A) Sydney GII.4 strain (GenBank accession no. JX459908); B) GII.4 San Francisco strain. The 3-dimensional structure models were predicted by using ChimeraX version 1.4 (11) and the alphafold prediction tool (12). Models show structural changes near and within the epitope A antigenic region on GII.4 San Francisco P-domain (panel B) are overlayed on a GII.4 Sydney 2012 backbone (Protein Data Bank, https://www.rcsb.org/structure/4OP7). Negatively (red) and positively (green) charged amino acids of GII.4 Sydney (panel A) were replaced with neutral amino acids (blue) in the GII.4 San Francisco strain and a hydrophobic (yellow) amino acid, alanine, was inserted between T293 and T294.