Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

• Type of Material: Article
• Authors: Liya Hu, Baylor College of Medicine; Sasirekha Ramani, Baylor College of Medicine; Rita Czako, Baylor College of Medicine; Banumathi Sankaran, Lawrence Berkeley National Laboratory; Ying Yu, Emory University; David Smith, Emory University; Richard Cummings, Emory University; Mary K. Estes, Baylor College of Medicine; B. V. Venkataram Prasad, Baylor College of Medicine
• Language: English
• Date: 2015-09-30
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms9346
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 6
• Start Page: 8346
• End Page: 8346
• Grant/Funding Information: The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under Contract No. DE-AC02-05CH11231.; We are thankful for support from NIH grants, AI36040 (to B.V.V.P.), AI 080656, AI 105101 and P30 DK56338 (to M.K.E.), GM098791 and P41GM103694 (to R.D.C.), that also supported D.F.S. and Y.Y. and the Robert Welch foundation (Q1279) to B.V.V.P.; The Berkeley Center for Structural Biology is supported in part by the NIH, National Institute of General Medical Sciences, and the Howard Hughes Medical Institute.
• Research Categories: Biology, Microbiology; Chemistry, Biochemistry; Biology, Virology

Abstract

© 2015 Macmillan Publishers Limited. Strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8∗ domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8∗ of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type II precursor glycans, and to restrict type II glycan binding in the bovine counterpart. Such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.