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Structure of human Aichi virus and implications for receptor binding

Nature Microbiology volume 1, Article number: 16150 (2016) | Download Citation


Aichi virus (AiV), an unusual and poorly characterized picornavirus, classified in the genus Kobuvirus, can cause severe gastroenteritis and deaths in children below the age of five years, especially in developing countries1,2. The seroprevalence of AiV is approximately 60% in children under the age of ten years and reaches 90% later in life3,4. There is no available vaccine or effective antiviral treatment. Here, we describe the structure of AiV at 3.7 Å. This first high-resolution structure for a kobuvirus is intermediate between those of the enteroviruses and cardioviruses, with a shallow, narrow depression bounded by the prominent VP0 CD loops (linking the C and D strands of the β-barrel), replacing the depression known as the canyon, frequently the site of receptor attachment in enteroviruses. VP0 is not cleaved to form VP2 and VP4, so the ‘VP2’ β-barrel structure is complemented with a unique extended structure on the inside of the capsid. On the outer surface, a polyproline helix structure, not seen previously in picornaviruses is present at the C terminus of VP1, a position where integrin binding motifs are found in some other picornaviruses. A peptide corresponding to this polyproline motif somewhat attenuates virus infectivity, presumably blocking host-cell attachment. This may guide cellular receptor identification.

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The authors thank Jun Dong and J. Diprose for IT support, the OPIC electron microscopy facility for microscope provision and Kai Zhang for data processing. Work was supported by the Ministry of Science and Technology 973 Project (grant no. 2014CB542800), the National Science Foundation (grant nos. 31570717 and 81520108019), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB08020200) and the MRC (grant nos. G100099 and MR/N00065X/1). The work of the Wellcome Trust Centre in Oxford is supported by Wellcome Trust core award 090532/Z/07/Z. The OPIC electron microscopy facility was founded by a Wellcome Trust JIF award (060208/Z/00/Z) and is supported by a Wellcome Trust equipment grant (093305/Z/10/Z). The Wellcome Trust, MRC and BBSRC also support the National EM facility, which enabled provision of the K2 detector. The Pirbright Institute receives strategic funding from the BBSRC. J.R. is Wellcome Trust-supported, E.E.F. and D.I.S. are supported by the MRC (grant no. G100099), and D.I.S. is supported as a Jenner Investigator.

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Author notes

    • Ling Zhu
    •  & Xiangxi Wang

    These authors contributed equally to this work.


  1. Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK

    • Ling Zhu
    • , Jingshan Ren
    • , Abhay Kotecha
    • , Thomas S. Walter
    • , Elizabeth E. Fry
    •  & David I. Stuart
  2. The Pirbright Institute, Pirbright, Surrey GU24 0NF, UK

    • Ling Zhu
    •  & Tobias J. Tuthill
  3. National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China

    • Xiangxi Wang
    • , Shuai Yuan
    •  & Zihe Rao
  4. Department of Microbiology and Medical Zoology, Aichi Prefectural Institute of Public Health, Aichi 4628576, Japan

    • Teruo Yamashita
  5. Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China

    • Zihe Rao
  6. Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK

    • David I. Stuart


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L.Z., X.W., T.S.W. and T.Y. prepared samples, L.Z., X.W., S.Y., A.K., J.R., T.J.T. and T.S.W. assisted in research. X.W., E.E.F., T.J.T. and D.I.S. designed the study. All authors analysed data. X.W., L.Z., J.R., E.E.F., Z.R. and D.I.S. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Zihe Rao or David I. Stuart.

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