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The Functional Characterization of Bat and Human P[3] Rotavirus VP8*s.
Dandi Li1,2, Mengxuan Wang1,2, Tongyao Mao1,2
1National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China.
Virologica Sinica
|May 31, 2021
Summary
P[3] rotavirus (RV) VP8* proteins from humans and dogs bind sialic acid, unlike bat RV. A specific mutation (C189Y) in bat VP8* enabled binding, suggesting residue 189 is key for rotavirus host jumping.
Area of Science:
- Virology
- Structural Biology
- Glycobiology
Background:
- P[3] rotavirus (RV) infects various species, utilizing glycans like sialic acid and histo-blood group antigens (HBGAs) for attachment.
- Understanding rotavirus VP8* protein interactions with glycans is crucial for comprehending host specificity and transmission.
Purpose of the Study:
- To investigate the glycan binding specificities of P[3] rotavirus VP8* proteins from different species.
- To identify key residues involved in glycan recognition and potential cross-species transmission.
Main Methods:
- Analysis of glycan binding specificity of human, dog, and bat P[3] RV VP8* proteins.
- Hemagglutination assays to assess red blood cell binding.
- Site-directed mutagenesis to create VP8* variants (C189Y and Y189C).
- Sequence alignment and structural analysis of VP8* proteins.
Main Results:
- Human and dog P[3] RV VP8* proteins recognized sialic acid-containing glycans and caused hemagglutination.
- Bat P[3] RV VP8* showed no glycan binding or hemagglutination.
- The bat P[3] VP8* C189Y mutant gained hemagglutination ability, while human P[3] VP8* Y189C mutants lost it.
- Residue 189 was identified as critical for ligand recognition and potential cross-species transmission.
- Structural differences in bat P[3] VP8* compared to simian RRV P[3] VP8* suggest distinct binding properties.
Conclusions:
- Residue 189 of P[3] RV VP8* plays a significant role in glycan binding and may influence host-species transmission.
- Bat P[3] rotavirus exhibits distinct glycan binding characteristics, potentially limiting its transmission to certain hosts.
- These findings enhance understanding of P[3] VP8*/glycan interactions and the transmission dynamics of bat and human rotaviruses.
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