Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens

Abstract

Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor–binding domains together with Lewis epitope–containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ββ and βα HBGA receptor–binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.

Emerging viruses: Cross-species transmission of coronaviruses, filoviruses, henipaviruses, and rotaviruses from bats

“…Based on nucleotide sequence identities in VP7 and VP4 genes, RVA is further classified into G and P genotypes, respectively. The P[8], P[4], and P[6] genotypes in the P[II] genogroup are responsible for over 90% of human infections worldwide, and are considered to have originated from P [I] RVs with an animal host origin and evolved the ability to infect humans (Xu et al, 2021). Currently, RVs have been reported from a variety of bat species belonging to Rhinolophidae, Vespertilionidae, Hipposideridae, Pteropodidae, Emballonuridae, and Rhinopomatidae (Esona et al, 2010;He et al, 2013He et al, , 2017Mishra et al, 2019;Waruhiu et al, 2017;Xia et al, 2014).…”

“…Li et al (2021) reported that the single amino acid mutation in the VP8* protein of bat P [3] genotype rotavirus obtained the ability to hemagglutinate the red blood cells, and this residue played an important role in the ligand recognition and may contribute to the cross-species transmission. However, other specific glycans, such as mucin and histo-blood group antigens (HBGAs), can interact with VP8* and affect RVs tropism in different hosts (Xu et al, 2021). Thus, the role of species-specific glycans in the cross-species transmission need to be further determined, which is of great significance for determining host range and epidemiology, species barrier mechanism, and cross-species transmission.…”

Serological Humoral Immunity Following Natural Infection of Children with High Burden Gastrointestinal Viruses

“…A more recent study provided structural evidence for the interactions of the P [8] genotype with the secretor HBGA precursor, but binding experiments did not support interactions with Lewis A or B HBGAs [7]. Further structural studies proposed the hypothesis that evolution of genogroup P[II] RV (P [8], P [4] and P [6]) progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs [66].These laboratory observations have been supported by epidemiological studies showing that P [8] and P [4] genotypes infect Lewis B secretor children preferentially and P [6] infects Lewis-negative children preferentially, irrespective of the secretor phenotype [6,[67][68][69][70]. The rotavirus P [6] genotype is more prevalent in sub-Saharan African and South-East Asian countries than in other populations, coinciding with a higher proportion of Lewis-negative phenotypes, reaching up to 30% of this population [60,68,71,72].…”

The Role of Host Glycobiology and Gut Microbiota in Rotavirus and Norovirus Infection, an Update

“…VP8* from P [8], P [4], P [6], P [14], P [11], and P [19] genotypes recognize the secretor HBGAs. Regarding P [8] and P [4] genotypes, there were controversial studies since some determined that they bind the Le b and H type-1 [25][26][27][28], while others report no Le b binding for these genotypes [29,30]. P [6] binds the H1 antigen but was reported not to bind Le b [31], whereas P [19] binds mucin core glycans with the GlcNAc-β-1→6-GalNAc motif and the type-1 HBGA precursor [32].…”

“…P [6] binds the H1 antigen but was reported not to bind Le b [31], whereas P [19] binds mucin core glycans with the GlcNAc-β-1→6-GalNAc motif and the type-1 HBGA precursor [32]. Other studies also documented that P [9], P [14], and P [25] strains interact with the A antigen [24,33], whereas P [11] interacts with single and repeated Nacetyl-lactosamine, the type-2 precursor glycan [34]. The HBGAs interactions with VP8* have been investigated by X-ray crystallography in some cases, identifying sugar binding pockets which are different from the sialic acid binding site identified in animal RV [30].…”