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.
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http://dx.doi.org/10.1073/pnas.2107963118 | DOI Listing |
PLoS Comput Biol
January 2025
Laboratoire de physique de l'École Normale Supérieure, CNRS, PSL University, Sorbonne Université, and Université de Paris, Paris, France.
T cells recognize a wide range of pathogens using surface receptors that interact directly with peptides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.
View Article and Find Full Text PDFNanocatalytic medicine for treating cancer requires effective, versatile and novel tools and approaches to significantly improve the therapeutic efficiency for the interactions of (non-)enzymatic reactions. However, it is necessary to develop (non-)enzymatic nanotechnologies capable of selectively killing tumour cells without harming normal cells. Their therapeutic characteristics should be the adaption of tumours' extra- and intracellular environment to being specifically active.
View Article and Find Full Text PDFCurr Pharm Des
January 2025
Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Metabolic Diseases, College of Life Sciences, Anhui Normal University, Wuhu 241000, Anhui, China.
Klebsiella pneumoniae (KP) is a common and highly pathogenic pathogen, which often causes several serious infections in humans. The rampant and inappropriate use of broad-spectrum antibiotics has fueled a worrisome surge in Multidrug Resistance (MDR) among the strains of K. pneumoniae, which has significantly boosted the risk and complexity of nosocomial infection transmission in clinical settings.
View Article and Find Full Text PDFMicrobiome
January 2025
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Background: Accurate classification of host phenotypes from microbiome data is crucial for advancing microbiome-based therapies, with machine learning offering effective solutions. However, the complexity of the gut microbiome, data sparsity, compositionality, and population-specificity present significant challenges. Microbiome data transformations can alleviate some of the aforementioned challenges, but their usage in machine learning tasks has largely been unexplored.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Virus Research Laboratory, ICMR-National Institute of Cholera and Enteric Disease, Kolkata 700010, India. Electronic address:
Human cytomegalovirus (HCMV) is a common herpesvirus that can severely affect transplant recipients, those with AIDS, and newborns. Existing synthetic medications face limitations, including toxicity, processing issues, and viral resistance. As part of this study, the efficacy of the extracellular enzyme laccase isolated from a widely available mushroom (Pleurotus pulmonarius) was compared to that of ganciclovir, a common antiviral, used against HCMV.
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