Patterns and Temporal Dynamics of Natural Recombination in Noroviruses

Abstract

Noroviruses infect a wide range of mammals and are the major cause of gastroenteritis in humans. Recombination at the junction of ORF1 encoding nonstructural proteins and ORF2 encoding major capsid protein VP1 is a well-known feature of noroviruses. Using all available complete norovirus sequences, we systematically analyzed patterns of natural recombination in the genus Norovirus both throughout the genome and across the genogroups. Recombination events between nonstructural (ORF1) and structural genomic regions (ORF2 and ORF3) were found in all analyzed genogroups of noroviruses, although recombination was most prominent between members of GII, the most common genogroup that infects humans. The half-life times of recombinant forms (clades without evidence of recombination) of human GI and GII noroviruses were 10.4 and 8.4–11.3 years, respectively. There was evidence of many recent recombination events, and most noroviruses that differed by more than 18% of nucleotide sequence were recombinant relative to each other. However, there were no distinct recombination events between viruses that differed by over 42% in ORF2/3, consistent with the absence of systematic recombination between different genogroups. The few inter-genogroup recombination events most likely occurred between ancient viruses before they diverged into contemporary genogroups. The recombination events within ORF1 or between ORF2/3 were generally rare. Thus, noroviruses routinely exchange full structural and nonstructural blocks of the genome, providing a modular evolution.

The International Virus Bioinformatics Meeting 2023

“…In picornaviruses, there was frequent recombination within the nonstructural genome region with no prominent hotspots and almost absent recombination within the structural genome region. Caliciviruses routinely exchanged full structural and nonstructural blocks of the genome, but had few, if any, recombination events within these regions [ 73 ]. In astroviruses, moderate recombination was observed within both structural and nonstructural genomic regions.…”

Genetic diversity and distribution of noroviruses among all age groups of patients with diarrhea in Amhara National Regional State, Ethiopia

“…The ORF-1 encodes six non-structural proteins including the RNA-dependent RNA polymerase (RdRp), whereas ORF-2 and ORF-3 encode the major capsid protein (VP1) and minor capsid protein, respectively [ 6 ]. Genetic recombination and mutation are responsible for the existing diversity of NoVs [ 7 ]. Based on the variations on the VP1 region, NoVs are classified into 10 genogroups (GI-GX) and 49 genotypes, with genogroups I and II being frequent causes of infection in humans and NoV GIV rarely [ 8 ].…”

Changing predominance of norovirus strains in children with acute gastroenteritis in Shanghai, 2018–2021

“…Of these, the GI, GII, GIV, GVIII and GIX groups can infect humans and cause AGE, with GI and GII are the most predominant genogroups associated with AGE in humans. Recently, a large number of studies have shown that NoV recombination often occurs near or within the ORF1 (RdRp)/ORF2 (VP1) junction, leading to the emergence of various recombinant strains worldwide ( Kendra et al., 2022 ; Zheng et al., 2022 ; Vakulenko et al., 2023 ). For example, the recombinant NoV GII.2[P16] associated with AGE emerged in 2016–2017 and spread across Europe and many countries in Asia ( Lu et al., 2017 ; Parra, 2019 ; Wang et al., 2021 ).…”