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Structural basis of rotavirus strain preference toward N-acetyl-or N-glycolylneuraminic acid-containing receptors

Journal Article


Abstract


  • The rotavirus spike protein domain VP8* is essential for recognition of cell surface carbohydrate receptors, notably those incorporatingN-acylneuraminic acids (members of the sialic acid family). N-Acetylneuraminic acids occur naturally in both animalsand humans, whereas N-glycolylneuraminic acids are acquired only through dietary uptake in normal human tissues. The preferenceof animal rotaviruses for these natural N-acylneuraminic acids has not been comprehensively established, and detailedstructural information regarding the interactions of different rotaviruses with N-glycolylneuraminic acids is lacking. In thisstudy, distinct specificities of VP8* for N-acetyl and N-glycolylneuraminic acids werrevealed using biophysical techniques. VP8* protein from the porcine rotavirus CRW-8 and the bovine rotavirus Nebraska clf diarrhea virus (NCDV) showed a preferencefor N-glycolyl-over N-acetylneuraminic acids, in contrast to results obtained with rhesus rotavirus (RRV). Crystallographicstructures of VP8* from CRW-8 and RRV with bound methyl-N-glycolylneuraminide revealed the atomic details of their interactions.We examined the influence of amino acid type at position 157, which is proximal to the ligand's N-acetyl or N-glycolylmoiety and can mutate upon cell culture adaptation. A structure-based hypothesis derived from these results could account forrotavirus discrimination between the N-acylneuraminic acid forms. Infectivity blockade experiments demonstrated that the determinedcarbohydrate specificities of these VP8* domains directly correlate with those of the corresponding infectious virus.This includes an association between CRW-8 adaption to cell culture, decreasedcompetition by N-glycolylneuraminic acid forCRW-8 infectivity, and a Pro157-to-Ser157 mutation in VP8*that reduces binding affinity for N-glycolylneuraminic acid. © 2012, American Society for Microbiology.

UOW Authors


  •   Blanchard, Helen (external author)

Publication Date


  • 2012

Citation


  • Yu, X., Dang, V. T., Fleming, F. E., von Itzstein, M., Coulson, B. S., & Blanchard, H. (2012). Structural basis of rotavirus strain preference toward N-acetyl-or N-glycolylneuraminic acid-containing receptors. Journal of Virology, 86(24), 13456-13466. doi:10.1128/JVI.06975-11

Scopus Eid


  • 2-s2.0-84870681494

Start Page


  • 13456

End Page


  • 13466

Volume


  • 86

Issue


  • 24

Abstract


  • The rotavirus spike protein domain VP8* is essential for recognition of cell surface carbohydrate receptors, notably those incorporatingN-acylneuraminic acids (members of the sialic acid family). N-Acetylneuraminic acids occur naturally in both animalsand humans, whereas N-glycolylneuraminic acids are acquired only through dietary uptake in normal human tissues. The preferenceof animal rotaviruses for these natural N-acylneuraminic acids has not been comprehensively established, and detailedstructural information regarding the interactions of different rotaviruses with N-glycolylneuraminic acids is lacking. In thisstudy, distinct specificities of VP8* for N-acetyl and N-glycolylneuraminic acids werrevealed using biophysical techniques. VP8* protein from the porcine rotavirus CRW-8 and the bovine rotavirus Nebraska clf diarrhea virus (NCDV) showed a preferencefor N-glycolyl-over N-acetylneuraminic acids, in contrast to results obtained with rhesus rotavirus (RRV). Crystallographicstructures of VP8* from CRW-8 and RRV with bound methyl-N-glycolylneuraminide revealed the atomic details of their interactions.We examined the influence of amino acid type at position 157, which is proximal to the ligand's N-acetyl or N-glycolylmoiety and can mutate upon cell culture adaptation. A structure-based hypothesis derived from these results could account forrotavirus discrimination between the N-acylneuraminic acid forms. Infectivity blockade experiments demonstrated that the determinedcarbohydrate specificities of these VP8* domains directly correlate with those of the corresponding infectious virus.This includes an association between CRW-8 adaption to cell culture, decreasedcompetition by N-glycolylneuraminic acid forCRW-8 infectivity, and a Pro157-to-Ser157 mutation in VP8*that reduces binding affinity for N-glycolylneuraminic acid. © 2012, American Society for Microbiology.

UOW Authors


  •   Blanchard, Helen (external author)

Publication Date


  • 2012

Citation


  • Yu, X., Dang, V. T., Fleming, F. E., von Itzstein, M., Coulson, B. S., & Blanchard, H. (2012). Structural basis of rotavirus strain preference toward N-acetyl-or N-glycolylneuraminic acid-containing receptors. Journal of Virology, 86(24), 13456-13466. doi:10.1128/JVI.06975-11

Scopus Eid


  • 2-s2.0-84870681494

Start Page


  • 13456

End Page


  • 13466

Volume


  • 86

Issue


  • 24