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Relative roles of GM1 ganglioside, N-acylneuraminic acids, and a2ß1 integrin in mediating rotavirus infection

Journal Article


Abstract


  • N-acetyl- and N-glycolylneuraminic acids (Sia) and α2β1 integrin are frequently used by rotaviruses as cellular receptors through recognition by virion spike protein VP4. The VP4 subunit VP8*, derived from Wa rotavirus, binds the internal N-acetylneuraminic acid on ganglioside GM1. Wa infection is increased by enhanced internal Sia access following terminal Sia removal from main glycan chains with sialidase. The GM1 ligand cholera toxin B (CTB) reduces Wa infectivity. Here, we found sialidase treatment increased cellular GM1 availability and the infectivity of several other human (including RV-3) and animal rotaviruses, typically rendering them susceptible to methyl α-D-N-acetylneuraminide treatment, but did not alter α2β1 usage. CTB reduced the infectivity of these viruses. Aceramido-GM1 inhibited Wa and RV-3 infectivity in untreated and sialidasetreated cells, and GM1 supplementation increased their infectivity, demonstrating the importance of GM1 for infection. Wa recognition of α2β1 and internal Sia were at least partially independent. Rotavirus usage of GM1 was mapped to VP4 using virus reassortants, and RV-3 VP8* bound aceramido-GM1 by saturation transfer difference nuclear magnetic resonance (STD NMR). Most rotaviruses recognizing terminal Sia did not use GM1, including RRV. RRV VP8* interacted minimally with aceramido- GM1 by STD NMR. Unusually, TFR-41 rotavirus infectivity depended upon terminal Sia and GM1. Competition of CTB, Sia, and/or aceramido-GM1 with cell binding by VP8* from representative rotaviruses showed that rotavirus Sia and GM1 preferences resulted from VP8*-cell binding. Our major finding is that infection by human rotaviruses of commonly occurring VP4 serotypes involves VP8* binding to cell surface GM1 glycan, typically including the internal N-acetylneuraminic acid. © 2014, American Society for Microbiology.

UOW Authors


  •   Blanchard, Helen (external author)

Publication Date


  • 2014

Citation


  • Fleming, F. E., Böhm, R., Dang, V. T., Holloway, G., Haselhorst, T., Madge, P. D., . . . Coulson, B. S. (2014). Relative roles of GM1 ganglioside, N-acylneuraminic acids, and a2ß1 integrin in mediating rotavirus infection. Journal of Virology, 88(8), 4558-4571. doi:10.1128/JVI.03431-13

Scopus Eid


  • 2-s2.0-84896971905

Start Page


  • 4558

End Page


  • 4571

Volume


  • 88

Issue


  • 8

Abstract


  • N-acetyl- and N-glycolylneuraminic acids (Sia) and α2β1 integrin are frequently used by rotaviruses as cellular receptors through recognition by virion spike protein VP4. The VP4 subunit VP8*, derived from Wa rotavirus, binds the internal N-acetylneuraminic acid on ganglioside GM1. Wa infection is increased by enhanced internal Sia access following terminal Sia removal from main glycan chains with sialidase. The GM1 ligand cholera toxin B (CTB) reduces Wa infectivity. Here, we found sialidase treatment increased cellular GM1 availability and the infectivity of several other human (including RV-3) and animal rotaviruses, typically rendering them susceptible to methyl α-D-N-acetylneuraminide treatment, but did not alter α2β1 usage. CTB reduced the infectivity of these viruses. Aceramido-GM1 inhibited Wa and RV-3 infectivity in untreated and sialidasetreated cells, and GM1 supplementation increased their infectivity, demonstrating the importance of GM1 for infection. Wa recognition of α2β1 and internal Sia were at least partially independent. Rotavirus usage of GM1 was mapped to VP4 using virus reassortants, and RV-3 VP8* bound aceramido-GM1 by saturation transfer difference nuclear magnetic resonance (STD NMR). Most rotaviruses recognizing terminal Sia did not use GM1, including RRV. RRV VP8* interacted minimally with aceramido- GM1 by STD NMR. Unusually, TFR-41 rotavirus infectivity depended upon terminal Sia and GM1. Competition of CTB, Sia, and/or aceramido-GM1 with cell binding by VP8* from representative rotaviruses showed that rotavirus Sia and GM1 preferences resulted from VP8*-cell binding. Our major finding is that infection by human rotaviruses of commonly occurring VP4 serotypes involves VP8* binding to cell surface GM1 glycan, typically including the internal N-acetylneuraminic acid. © 2014, American Society for Microbiology.

UOW Authors


  •   Blanchard, Helen (external author)

Publication Date


  • 2014

Citation


  • Fleming, F. E., Böhm, R., Dang, V. T., Holloway, G., Haselhorst, T., Madge, P. D., . . . Coulson, B. S. (2014). Relative roles of GM1 ganglioside, N-acylneuraminic acids, and a2ß1 integrin in mediating rotavirus infection. Journal of Virology, 88(8), 4558-4571. doi:10.1128/JVI.03431-13

Scopus Eid


  • 2-s2.0-84896971905

Start Page


  • 4558

End Page


  • 4571

Volume


  • 88

Issue


  • 8