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GANo

Welcome to GANo (Genetic and Antigenic Evolution of Noroviruses). GANo is a platform that provides curated and comprehensive databases for visualization and analysis of norovirus genetic and antigenic diversification [1]. The datasets used are updated versions of our previous work, which includes the analysis of all publicly available norovirus sequences [1,2,3,4]. To keep up with this fast-evolving virus, we will continually be updating (ad hoc) these databases from publicly available sequence information.

The extreme genetic and antigenic diversity presented by noroviruses is one of the major obstacles for the development of vaccines and specific therapeutics. To aid in the understanding of norovirus epidemiology, disease, and vaccine design, GANo provides two tools for the analyses of this diversification:

Genotype Tracker GII.4 Epitope Tracker

1. Genotype and Variant Spatiotemporal Distribution [Genotype Tracker]: This tool provides a graphical visualization of our previous work [2], which allows the quantification of global and regional circulation trends of each genotype and their recombinant forms.

Figure 1, screenshot from the app showing genotype temporal distribution
Figure 1: Temporal distribution of circulating norovirus capsid genotypes between 1995 to 2022. Genotype identification was done using sequences that sufficiently covered capsid regions that could be used for genotyping. The dataset used was updated from that of Kendra et al. [2].

2. Antigenic Site Diversification of GII.4 Norovirus [GII.4 Epitope Tracker]: The most predominant norovirus genotype, GII.4, presents variable antigenic sites on the top of the viral capsid protein. Continued variation on these antigenic sites has been shown to correlate with variant emergence and immune evasion to previous infections (Figure 2). This tool provides a graphical visualization of the genetic variability of each of these antigenic sites as well as any other residue from the norovirus major capsid protein.

Figure 2, norovirus virion, P domain with antigenic sites, variants temporal distribution
Figure 2: Structural model of the norovirus virion. (A) The virion is composed of 180 copies of the major capsid protein (VP1), arranged in a T=3 icosahedral array. (B) VP1 is structurally divided in two domains: Protruding and Shell. (C) The variable antigenic sites and Histo-blood group antigen (HBGA) carbohydrate binding sites are located in the Protruding domain and neutralizing antibodies map to these sites [3, 5]. (D) Temporal distribution of GII.4 variants [3, 5]. Most differences among the variants map to the variable antigenic sites. The structural models were rendered using protein data bank (PDB) files: 1IHM and 4OPS.

We expect this application will assist our colleagues working on molecular epidemiology, therapeutics, and vaccines for human noroviruses to assess the relevance of their findings in the context of historical diversification of human noroviruses.

Citations and References:

  1. [Placeholder R Shiny app description]

  2. Global and regional circulation trends of norovirus genotypes and recombinants, 1995-2019: A comprehensive review of sequences from public databases. Kendra JA, Tohma K, Parra GI. Rev Med Virol. 2022 Sep;32(5):e2354. doi: 10.1002/rmv.2354.

  3. Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains. Tohma K, Lepore CJ, Gao Y, Ford-Siltz LA, Parra GI. mBio. 2019 Sep 24;10(5):e02202-19. doi: 10.1128/mBio.02202-19.

  4. Minimal Antigenic Evolution after a Decade of Norovirus GII.4 Sydney_2012 Circulation in Humans. Parra GI, Tohma K, Ford-Siltz LA, Eguino P, Kendra JA, Pilewski KA, Gao Y. J Virol. 2023 Feb 28;97(2):e0171622. doi: 10.1128/jvi.01716-22.

  5. Dynamic immunodominance hierarchy of neutralizing antibody responses to evolving GII.4 noroviruses. Tohma K, Ford-Siltz LA, Kendra JA, Parra GI. Cell Rep. 2022 Apr 12;39(2):110689

    6. For questions or comments about GANo, please contact Dr. Gabriel I Parra: gabriel.parra@fda.hhs.gov.