Biology subjects

Gozalbo-Rovira, R.

Publications and source records attributed to Gozalbo-Rovira, R..

4 recordsLinked to original sources

bioRxiv2025

Deciphering the role of histo-blood group antigens in bovine rotavirus C infection

Rotaviruses (RVs) are the main cause of viral diarrhea among infants, small children, and the young of many animal species. Histo-blood group antigens (HBGAs) are potential RV receptors and glycan composition on mucous surfaces influences host susceptibility and cross-species virus transmission. RVs exhibit genotype-dependent glycan binding and differences are due to sequence modifications in the VP8* domain of the spike protein VP4. Nevertheless, the molecular bases for this genotype-dependent glycan specificity, especially in non-A RVs, are not thoroughly understood. This study delves into how genotypic variations configure a novel binding site in the VP8* of a bovine P[3] rotavirus species C (RVC) strain to recognize H type-2 antigen (H2) and its precursor N-acetyl-lactosamine (LacNAc) using glycan binding assays, crystallography, and STD NMR. Results reveal a specific interaction of bovine P[3] RVC VP8* with H2 and LacNAc, more strongly with the latter. In the P[3] RVC VP8*-H2 interaction, the N-acetyl glucosamine moiety displays significant interaction, while galactose participates moderately and fucose binds weakly. Moreover, the bovine VP8* structure, resolved at 3 [A], shows specific structural features which differ from human RVC, as it contains two additional {beta}-strands ({beta}1 and {beta}2) contributing to {beta}-sheet2 and conformational changes that widens the cleft to allow different carbohydrate binding modes. These subtle changes in both sequence and structure explain the H2 precursor recognition, which is ubiquitous in human neonate intestine and in human and bovine milk, providing insights into P[3] RVC tropism and its potential zoonotic transmission. Author SummaryRotavirus C (RVC) represents an emerging pathogen with the ability to infect both humans and animals. It is widely acknowledged that host glycobiology plays a crucial role in determining susceptibility to RVs. Consequently, a better understanding of the interactions between RVs and carbohydrates is essential to know how the virus causes infection and to develop effective preventive strategies. Recent findings have unveiled the capability of the human RVC genotype P[2] to recognize the type A antigen through the VP8* spike protein although little is known about animal RVC strains. In this study, we describe the capacity of bovine P[3] RVC strain to bind H2 and LacNAc, both HBGAs. We also offer the structural explanation for the glycan differential recognition between human and bovine RVC strains. Our findings offer valuable insights into RVC attachment to host cells and its potential implications for species barriers.

microbiology↗

bioRxiv2021

Wide Diversity of Recombinant Noroviruses Circulating in Spain, 2016 to 2020

Noroviruses are the leading cause of sporadic cases and outbreaks of viral gastroenteritis. For more than 20 years most norovirus infections have been caused by the pandemic genotype GII.4, yet recent studies have reported the emergence of recombinant strains in many countries. In the present study, 4,950 stool samples collected between January 2016 and April 2020 in Valencia (Spain) from patients with acute gastroenteritis were analyzed to investigate the etiological agent. Norovirus was the most frequently detected enteric virus with a positive rate of 9.5% (471/4,950). Among 224 norovirus strains characterized, 175 belonged to genogroup GII and 49 to genogroup GI. Using dual genotyping based on sequencing the ORF1/ORF2 junction region we detected 25 different capsid-polymerase type associations. The most common GII capsid genotype was GII.4 Sydney 2012, followed by GII.2, GII.3, GII.6 and GII.17. A high prevalence of recombinant strains (90.4%) was observed among GII infections between 2018 and 2020. GII.4 Sydney[P16] was the predominant genotype from 2019 to 2020. In addition, GII.P16 polymerase was found harboring within six different capsid genes. A new subcluster of GII.4 Sydney associated with the P31 polymerase was identified by phylogenetic analysis. GI.4 and GI.3 were the predominant genotypes in genogroup GI, in which recombinant strains were also found, such as GI.3[P10], GI.3[P13] and GI.5[P4]. Interestingly, the GI.3[P10] strain could represent a new capsid genotype. This study shows the extensive diversity of recombinant noroviruses circulating in Spain and highlights the role of recombination events in the spread of noroviruses.

microbiology↗

bioRxiv2021

The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: the case of the spike A222V mutation

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has now reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.

molecular biology↗

bioRxiv2021

Microbiota depletion promotes human rotavirus replication in an adult mouse model

The study of human rotavirus (RV) infectivity in vivo has been limited by the lack of small animal models able to efficiently replicate the principal human RV genotypes. In recent years, intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of developing an adult mouse infection model for RV we performed faecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. Contrarily to control mice, in the FMT group, but also in antibiotic-treated mice without FMT, challenge with the human RV G1P[8] genotype, Wa strain (RVwa), resulted in viral shedding in the faeces for 6 days. RV titres in faeces were also significantly higher in antibiotic-treated animals with or without FMT. This excluded the hypothesis that donors microbiota promoted infection. Antibiotic treatment followed by self-FMT resulted in incomplete re-establishment of mouse microbiota which partially restored suppression of RVwa infection. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum and Oscillospira, reappeared after self-FMT. In antibiotic-treated and FMT animals, differences were observed in gene expression of immune mediators such as IL10, TNF- and IFN{gamma} and the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human RV infectivity in mice. Viral permissiveness could involve changes in the innate immune system at the small intestine and alterations in the bacteria population that potentially interact with RV, creating a favourable environment for human RV replication in mice.

microbiology↗