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Structure of human Aichi virus and implications for receptor binding

Abstract

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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Figure 1: The 3.68 Å resolution (overall) cryo-EM structure of AiV.
Figure 2: Overall structures, phylogeny and structural features.
Figure 3: Particle stability and the correlation between particle stability and interaction areas.
Figure 4: A proline-rich motif, a potential receptor binding site in AiV.

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Acknowledgements

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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Contributions

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.

Corresponding authors

Correspondence to Zihe Rao or David I. Stuart.

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Supplementary Figures 1–6, Supplementary Tables 1–3, Supplementary References (PDF 13044 kb)

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Zhu, L., Wang, X., Ren, J. et al. Structure of human Aichi virus and implications for receptor binding. Nat Microbiol 1, 16150 (2016). https://doi.org/10.1038/nmicrobiol.2016.150

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