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Assays for the Specific Growth Rate and Cell-binding Ability of Rotavirus
Published on: January 28, 2019
Novel structural insights into rotavirus recognition of ganglioside glycan receptors
Xing Yu1, Barbara S Coulson, Fiona E Fleming
1Institute for Glycomics, Gold Coast campus, Griffith University, Queensland 4222, Australia.
Insights
Rotaviruses attach to host cells using sialic acid-containing glycans. This study reveals the first atomic structures of rotavirus VP8* protein interacting with ganglioside G(M3) glycans, detailing this crucial viral attachment mechanism.
Area of Science:
- Virology
- Structural Biology
- Glycobiology
Background:
- Rotaviruses cause significant childhood diarrheal disease globally.
- Sialic acid-containing host cell oligosaccharides are essential for rotavirus attachment.
- Detailed atomic models of rotavirus-glycan interactions were previously lacking.
Purpose of the Study:
- To determine the first crystallographic structures of the rotavirus VP8* protein in complex with ganglioside G(M3) glycans.
- To elucidate the precise molecular interactions governing rotavirus recognition of glycoconjugate receptors.
- To correlate VP8* carbohydrate specificities with infectious rotavirus particle behavior.
Main Methods:
- X-ray crystallography to obtain atomic structures of VP8*-glycan complexes.
- Biochemical assays to assess the inhibition of rotavirus infectivity.
- Comparative analysis of VP8* specificities from different rotavirus strains.
Main Results:
- Presented the first atomic structures of rotavirus VP8* complexed with ganglioside G(M3) glycans.
- Revealed key molecular details of rotavirus-ganglioside G(M3) glycan recognition.
- Demonstrated a direct correlation between VP8* specificity and infectious virus particle behavior in porcine and monkey rotaviruses.
- Indicated potential binding interactions with other sialic acid-containing gangliosides.
Conclusions:
- The study provides unprecedented atomic insights into rotavirus attachment mechanisms.
- Understanding these interactions is crucial for developing targeted antiviral strategies.
- The findings pave the way for exploring broader rotavirus-glycan binding specificities.
Abstract:
Rotaviruses ubiquitously infect children under the age of 5, being responsible for more than half a million diarrhoeal deaths each year worldwide. Host cell oligosaccharides containing sialic acid(s) are critical for attachment by rotaviruses. However, to date, no detailed three-dimensional atomic model showing the exact rotavirus interactions with these glycoconjugate receptors has been reported. Here, we present the first crystallographic structures of the rotavirus carbohydrate-recognizing protein VP8* in complex with ganglioside G(M3) glycans. In combination with assessment of the inhibition of rotavirus infectivity by N-acetyl and N-glycolyl forms of this ganglioside, our results reveal key details of rotavirus-ganglioside G(M3) glycan recognition. In addition, they show a direct correlation between the carbohydrate specificities exhibited by VP8* from porcine and by monkey rotaviruses and the respective infectious virus particles. These novel results also indicate the potential binding interactions of rotavirus VP8* with other sialic acid-containing gangliosides.
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