@article{638fbdfcab1f48a5861fbd20399ba331,
title = "Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses",
abstract = "Diverse noroviruses infect humans and animals via the recognition of host-specific glycan ligands. Genogroup II (GII) noroviruses consist of human noroviruses (huNoVs) that generally bind histo-blood group antigens (HBGAs) as host factors and three porcine norovirus (porNoV) genotypes (GII.11/18/19) that form a genetic lineage lacking HBGA-binding ability. Thus, these GII porNoVs provide an excellent model to study norovirus evolution with host ligand specificity changes. Here we solved the crystal structures of a native GII.11 porNoV P protein and a closely-related GII.3 huNoV P protein complexed with an HBGA, focusing on the HBGA-binding sites (HBSs) compared with the previously known ones to understand the structural basis of the host ligand specificity change. We found that the GII.3 huNoV binds HBGAs via a conventional GII HBS that uses an arginine instead of the conserved aromatic residue for the required Van der Waals interaction, while the GII.11 porNoV HBS loses its HBGA-binding function because of two mutations (Q355/V451). A mutant that reversed the two mutated residues back to the conventional A355/Y451 restored the HBGA-binding function of the GII.11 porNoV P protein, which validated our observations. Similar mutations are also found in GII.19 porNoVs and a GII.19 P protein mutant with double reverse mutations restored the HBS function. This is the first reconstruction of a functional HBS based on one with new host specificity back to its parental one. These data shed light on the molecular basis of structural adaptation of the GII porNoVs to the pig hosts through mutations at their HBSs.",
keywords = "Emerging norovirus, crystal structure, viral attachment, viral evolution, viral receptor, virus-host interaction",
author = "Yang Yang and Ming Xia and Leyi Wang and Sahaana Arumugam and Yajing Wang and Xianjin Ou and Chenlong Wang and Xi Jiang and Ming Tan and Yutao Chen and Xuemei Li",
note = "Funding Information: The research described in this article was supported by the National Basic Research Program (973 Program, grant number 2017YFC0840301, 2016DDJ1ZZ17, and 2014CB542802), the National Natural Science Foundation of China (grant number 31670752), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant number XDB08020203) and to X.L and Y.C. This work was also supported by the National Institute of Health, the National Institute of Allergy and Infectious Diseases (R56AI114831 and R01 AI089634 to X. J. and 1R21AI097936-01A1 to M.T./Jarek Meller) and an institutional Innovation Fund of Cincinnati Children{\textquoteright}s Hospital Medical Center to M.T. We thank the staff of the beamline 17U at Shanghai Synchrotron Radiation Facility (SSRF) for technical assistance during X-ray diffraction data collection. We also thank the Core Facility in the Institute of Biophysics, Chinese Academy of Sciences (CAS) for technical support. Funding Information: The research described in this article was supported by the National Basic Research Program (973 Program, grant numbers: 2017YFC0840301, 2016DDJ1ZZ17, and 2014CB542802), the National Natural Science Foundation of China (grant number 31670752), Chinese Academy of Sciences (grant number XDB08020203) to X.L and Y.C. This work was also supported by the National Institute of Health, the National Institute of Allergy and Infectious Diseases (R56AI114831 and R01 AI089634 to X. J. and 1R21AI097936-01A1 to M.T./Jarek Meller); an institutional Innovation Fund of Cincinnati Children?s Hospital Medical Center to M.T.; and a TRG grant from the Center for Clinical and Translational Science, University of Cincinnati. The research described in this article was supported by the National Basic Research Program (973 Program, grant number 2017YFC0840301, 2016DDJ1ZZ17, and 2014CB542802), the National Natural Science Foundation of China (grant number 31670752), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant number XDB08020203) and to X.L and Y.C. This work was also supported by the National Institute of Health, the National Institute of Allergy and Infectious Diseases (R56AI114831 and R01 AI089634 to X. J. and 1R21AI097936-01A1 to M.T./Jarek Meller) and an institutional Innovation Fund of Cincinnati Children?s Hospital Medical Center to M.T. We thank the staff of the beamline 17U at Shanghai Synchrotron Radiation Facility (SSRF) for technical assistance during X-ray diffraction data collection. We also thank the Core Facility in the Institute of Biophysics, Chinese Academy of Sciences (CAS) for technical support. Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.",
year = "2019",
month = jan,
day = "1",
doi = "10.1080/22221751.2019.1686335",
language = "English (US)",
volume = "8",
pages = "1642--1657",
journal = "Emerging Microbes and Infections",
issn = "2222-1751",
publisher = "Nature Publishing Group",
number = "1",
}