1887

Abstract

Murine adenovirus 2 (MAdV-2) infects cells of the mouse gastrointestinal tract. Like human adenoviruses, it is a member of the genus Mastadenovirus, family Adenoviridae. The MAdV-2 genome has a single fibre gene that expresses a 787 residue-long protein. Through analogy to other adenovirus fibre proteins, it is expected that the carboxy-terminal virus-distal head domain of the fibre is responsible for binding to the host cell, although the natural receptor is unknown. The putative head domain has little sequence identity to adenovirus fibres of known structure. In this report, we present high-resolution crystal structures of the carboxy-terminal part of the MAdV-2 fibre. The structures reveal a domain with the typical adenovirus fibre head topology and a domain containing two triple β-spiral repeats of the shaft domain. Through glycan microarray profiling, saturation transfer difference nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and site-directed mutagenesis, we show that the fibre specifically binds to the monosaccharide N-acetylglucosamine (GlcNAc). The crystal structure of the complex reveals that GlcNAc binds between the AB and CD loops at the top of each of the three monomers of the MAdV-2 fibre head. However, infection competition assays show that soluble GlcNAc monosaccharide and natural GlcNAc-containing polymers do not inhibit infection by MAdV-2. Furthermore, site-directed mutation of the GlcNAc-binding residues does not prevent the inhibition of infection by soluble fibre protein. On the other hand, we show that the MAdV-2 fibre protein binds GlcNAc-containing mucin glycans, which suggests that the MAdV-2 fibre protein may play a role in viral mucin penetration in the mouse gut.

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2018-10-02
2019-09-23
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References

  1. Rowe WP, Huebner RJ, Gilmore LK, Parrott RH, Ward TG. Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med 1953;84:570–573 [CrossRef][PubMed]
    [Google Scholar]
  2. San Martín C. Latest insights on adenovirus structure and assembly. Viruses 2012;4:847–877 [CrossRef][PubMed]
    [Google Scholar]
  3. Yu X, Veesler D, Campbell MG, Barry ME, Asturias FJ et al. Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses. Sci Adv 2017;3:e1602670 [CrossRef][PubMed]
    [Google Scholar]
  4. Arnberg N. Adenovirus receptors: implications for targeting of viral vectors. Trends Pharmacol Sci 2012;33:442–448 [CrossRef][PubMed]
    [Google Scholar]
  5. Harrach B, Benkő M, Both GW, Brown M, Davison AJ et al. Family Adenoviridae. In King AM, Adams MJ, Carstens EB, Lefkowitz EJ. (editors) Virus Taxonomy: Classification and Nomenclature of Viruses. Ninth Report of the International Committee on Taxonomy of Viruses San Diego, CA: Elsevier; 2011; pp.125–141
    [Google Scholar]
  6. Hashimoto K, Sugiyama T, Sasaki S. An adenovirus isolated from the feces of mice I. Isolation and identification. Jpn J Microbiol 1966;10:115–125[PubMed]
    [Google Scholar]
  7. Takeuchi A, Hashimoto K. Electron microscope study of experimental enteric adenovirus infection in mice. Infect Immun 1976;13:569–580[PubMed]
    [Google Scholar]
  8. Sugiyama T, Hashimoto K, Sasaki S. An adenovirus isolated from the feces of mice. II. Experimental infection. Jpn J Microbiol 1967;11:33–42[PubMed]
    [Google Scholar]
  9. Wilson SS, Bromme BA, Holly MK, Wiens ME, Gounder AP et al. Alpha-defensin-dependent enhancement of enteric viral infection. PLoS Pathog 2017;13:e1006446 [CrossRef][PubMed]
    [Google Scholar]
  10. Hemmi S, Vidovszky MZ, Ruminska J, Ramelli S, Decurtins W et al. Genomic and phylogenetic analyses of murine adenovirus 2. Virus Res 2011;160:128–135 [CrossRef][PubMed]
    [Google Scholar]
  11. Meissner JD, Hirsch GN, Larue EA, Fulcher RA, Spindler KR. Completion of the DNA sequence of mouse adenovirus type 1: sequence of E2B, L1, and L2 (18-51 map units). Virus Res 1997;51:53–64 [CrossRef][PubMed]
    [Google Scholar]
  12. Klempa B, Krüger DH, Auste B, Stanko M, Krawczyk A et al. A novel cardiotropic murine adenovirus representing a distinct species of mastadenoviruses. J Virol 2009;83:5749–5759 [CrossRef][PubMed]
    [Google Scholar]
  13. Bewley MC, Springer K, Zhang YB, Freimuth P, Flanagan JM. Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. Science 1999;286:1579–1583 [CrossRef][PubMed]
    [Google Scholar]
  14. Burmeister WP, Guilligay D, Cusack S, Wadell G, Arnberg N. Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites. J Virol 2004;78:7727–7736 [CrossRef][PubMed]
    [Google Scholar]
  15. Persson BD, Schmitz NB, Santiago C, Zocher G, Larvie M et al. Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens. PLoS Pathog 2010;6:e1001122 [CrossRef][PubMed]
    [Google Scholar]
  16. Nilsson EC, Storm RJ, Bauer J, Johansson SM, Lookene A et al. The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis. Nat Med 2011;17:105–109 [CrossRef][PubMed]
    [Google Scholar]
  17. van Raaij MJ, Mitraki A, Lavigne G, Cusack S. A triple beta-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein. Nature 1999;401:935–938 [CrossRef][PubMed]
    [Google Scholar]
  18. Zubieta C, Schoehn G, Chroboczek J, Cusack S. The structure of the human adenovirus 2 penton. Mol Cell 2005;17:121–135 [CrossRef][PubMed]
    [Google Scholar]
  19. Liu H, Wu L, Zhou ZH. Model of the trimeric fiber and its interactions with the pentameric penton base of human adenovirus by cryo-electron microscopy. J Mol Biol 2011;406:764–774 [CrossRef][PubMed]
    [Google Scholar]
  20. Xia D, Henry LJ, Gerard RD, Deisenhofer J. Crystal structure of the receptor-binding domain of adenovirus type 5 fiber protein at 1.7 A resolution. Structure 1994;2:1259–1270 [CrossRef][PubMed]
    [Google Scholar]
  21. Seiradake E, Lortat-Jacob H, Billet O, Kremer EJ, Cusack S. Structural and mutational analysis of human Ad37 and canine adenovirus 2 fiber heads in complex with the D1 domain of coxsackie and adenovirus receptor. J Biol Chem 2006;281:33704–33716 [CrossRef][PubMed]
    [Google Scholar]
  22. Chappell JD, Prota AE, Dermody TS, Stehle T. Crystal structure of reovirus attachment protein sigma1 reveals evolutionary relationship to adenovirus fiber. EMBO J 2002;21:1–11 [CrossRef][PubMed]
    [Google Scholar]
  23. Guardado Calvo P, Fox GC, Hermo Parrado XL, Llamas-Saiz AL, Costas C et al. Structure of the carboxy-terminal receptor-binding domain of avian reovirus fibre sigmaC. J Mol Biol 2005;354:137–149 [CrossRef][PubMed]
    [Google Scholar]
  24. Merckel MC, Huiskonen JT, Bamford DH, Goldman A, Tuma R. The structure of the bacteriophage PRD1 spike sheds light on the evolution of viral capsid architecture. Mol Cell 2005;18:161–170 [CrossRef][PubMed]
    [Google Scholar]
  25. Wu E, Pache L, von Seggern DJ, Mullen TM, Mikyas Y et al. Flexibility of the adenovirus fiber is required for efficient receptor interaction. J Virol 2003;77:7225–7235 [CrossRef][PubMed]
    [Google Scholar]
  26. Hong JS, Engler JA. Domains required for assembly of adenovirus type 2 fiber trimers. J Virol 1996;70:7071–7078[PubMed]
    [Google Scholar]
  27. Persson BD, Reiter DM, Marttila M, Mei YF, Casasnovas JM et al. Adenovirus type 11 binding alters the conformation of its receptor CD46. Nat Struct Mol Biol 2007;14:164–166 [CrossRef][PubMed]
    [Google Scholar]
  28. Seiradake E, Henaff D, Wodrich H, Billet O, Perreau M et al. The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution. PLoS Pathog 2009;5:e1000277 [CrossRef][PubMed]
    [Google Scholar]
  29. Cupelli K, Müller S, Persson BD, Jost M, Arnberg N et al. Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses. J Virol 2010;84:3189–3200 [CrossRef][PubMed]
    [Google Scholar]
  30. Arnberg N, Kidd AH, Edlund K, Nilsson J, Pring-Akerblom P et al. Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction. Virology 2002;302:33–43 [CrossRef][PubMed]
    [Google Scholar]
  31. Lenman A, Liaci AM, Liu Y, Frängsmyr L, Frank M et al. Polysialic acid is a cellular receptor for human adenovirus 52. Proc Natl Acad Sci USA 2018;115:E4264E4273 [CrossRef][PubMed]
    [Google Scholar]
  32. Singh AK, Berbís , Ballmann MZ, Kilcoyne M, Menéndez M et al. Structure and sialyllactose binding of the carboxy-terminal head domain of the fibre from a siadenovirus, Turkey adenovirus 3. PLoS One 2015;10:e0139339 [CrossRef][PubMed]
    [Google Scholar]
  33. Parente JP, Wieruszeski JM, Strecker G, Montreuil J, Fournet B et al. A novel type of carbohydrate structure present in hen ovomucoid. J Biol Chem 1982;257:13173–13176[PubMed]
    [Google Scholar]
  34. Yamashita K, Kamerling JP, Kobata A. Structural study of the carbohydrate moiety of hen ovomucoid. Occurrence of a series of pentaantennary complex-type asparagine-linked sugar chains. J Biol Chem 1982;257:12809–12814[PubMed]
    [Google Scholar]
  35. Yamashita K, Kamerling JP, Kobata A. Structural studies of the sugar chains of hen ovomucoid. Evidence indicating that they are formed mainly by the alternate biosynthetic pathway of asparagine-linked sugar chains. J Biol Chem 1983;258:3099–3106[PubMed]
    [Google Scholar]
  36. Yet MG, Chin CC, Wold F. The covalent structure of individual N-linked glycopeptides from ovomucoid and asialofetuin. J Biol Chem 1988;263:111–117[PubMed]
    [Google Scholar]
  37. Gerlach JQ, Kilcoyne M, Eaton S, Bhavanandan V, Joshi L. Non-carbohydrate-mediated interaction of lectins with plant proteins. Adv Exp Med Biol 2011;705:257–269 [CrossRef][PubMed]
    [Google Scholar]
  38. Menéndez-Conejero R, Nguyen TH, Singh AK, Condezo GN, Marschang RE et al. Structure of a reptilian adenovirus reveals a phage tailspike fold stabilizing a vertebrate virus capsid. Structure 2017;25:1562–1573 [CrossRef][PubMed]
    [Google Scholar]
  39. Harvey DJ, Wing DR, Küster B, Wilson IB. Composition of N-linked carbohydrates from ovalbumin and co-purified glycoproteins. J Am Soc Mass Spectrom 2000;11:564–571 [CrossRef][PubMed]
    [Google Scholar]
  40. Chalkley RJ, Burlingame AL. Identification of novel sites of O-N-acetylglucosamine modification of serum response factor using quadrupole time-of-flight mass spectrometry. Mol Cell Proteomics 2003;2:182–190 [CrossRef][PubMed]
    [Google Scholar]
  41. Guardado-Calvo P, Muñoz EM, Llamas-Saiz AL, Fox GC, Kahn R et al. Crystallographic structure of porcine adenovirus type 4 fiber head and galectin domains. J Virol 2010;84:10558–10568 [CrossRef][PubMed]
    [Google Scholar]
  42. Lenman A, Liaci AM, Liu Y, Årdahl C, Rajan A et al. Human adenovirus 52 uses sialic acid-containing glycoproteins and the coxsackie and adenovirus receptor for binding to target cells. PLoS Pathog 2015;11:e1004657 [CrossRef][PubMed]
    [Google Scholar]
  43. Lundquist JJ, Toone EJ. The Cluster Glycoside Effect. Chem Rev 2002;102:555–578 [CrossRef]
    [Google Scholar]
  44. Lortat-Jacob H, Chouin E, Cusack S, van Raaij MJ. Kinetic analysis of adenovirus fiber binding to its receptor reveals an avidity mechanism for trimeric receptor-ligand interactions. J Biol Chem 2001;276:9009–9015 [CrossRef][PubMed]
    [Google Scholar]
  45. Jiménez-Moreno E, Jiménez-Osés G, Gómez AM, Santana AG, Corzana F et al. A thorough experimental study of CH/π interactions in water: quantitative structure-stability relationships for carbohydrate/aromatic complexes. Chem Sci 2015;6:6076–6085 [CrossRef][PubMed]
    [Google Scholar]
  46. Soudais C, Boutin S, Hong SS, Chillon M, Danos O et al. Canine adenovirus type 2 attachment and internalization: coxsackievirus-adenovirus receptor, alternative receptors, and an RGD-independent pathway. J Virol 2000;74:10639–10649 [CrossRef][PubMed]
    [Google Scholar]
  47. Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol 2016;16:639–649 [CrossRef][PubMed]
    [Google Scholar]
  48. Etzold S, Juge N. Structural insights into bacterial recognition of intestinal mucins. Curr Opin Struct Biol 2014;28:23–31 [CrossRef][PubMed]
    [Google Scholar]
  49. Kilcoyne M, Gerlach JQ, Gough R, Gallagher ME, Kane M et al. Construction of a natural mucin microarray and interrogation for biologically relevant glyco-epitopes. Anal Chem 2012;84:3330–3338 [CrossRef][PubMed]
    [Google Scholar]
  50. Smith AL, Barthold SW. Factors influencing susceptibility of laboratory rodents to infection with mouse adenovirus strains K87 and FL. Arch Virol 1987;95:143–148 [CrossRef][PubMed]
    [Google Scholar]
  51. di Paolo NC, Kalyuzhniy O, Shayakhmetov DM. Fiber shaft-chimeric adenovirus vectors lacking the KKTK motif efficiently infect liver cells in vivo. J Virol 2007;81:12249–12259 [CrossRef][PubMed]
    [Google Scholar]
  52. Tuve S, Wang H, Jacobs JD, Yumul RC, Smith DF et al. Role of cellular heparan sulfate proteoglycans in infection of human adenovirus serotype 3 and 35. PLoS Pathog 2008;4:e1000189 [CrossRef][PubMed]
    [Google Scholar]
  53. Holmén Larsson JM, Thomsson KA, Rodríguez-Piñeiro AM, Karlsson H, Hansson GC. Studies of mucus in mouse stomach, small intestine, and colon. III. Gastrointestinal Muc5ac and Muc2 mucin O-glycan patterns reveal a regiospecific distribution. Am J Physiol Gastrointest Liver Physiol 2013;305:G357–G363 [CrossRef][PubMed]
    [Google Scholar]
  54. Singh AK, Ballmann MZ, Benkő M, Harrach B, van Raaij MJ. Crystallization of the C-terminal head domain of the fibre protein from a siadenovirus, turkey adenovirus 3. Acta Cryst F 2013;69:1135–1139 [CrossRef][PubMed]
    [Google Scholar]
  55. Winter G. xia2 : an expert system for macromolecular crystallography data reduction. J Appl Cryst 2010;43:186–190 [CrossRef]
    [Google Scholar]
  56. Battye TG, Kontogiannis L, Johnson O, Powell HR, Leslie AG. iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Cryst D 2011;67:271–281 [CrossRef][PubMed]
    [Google Scholar]
  57. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P et al. Overview of the CCP4 suite and current developments. Acta Cryst D 2011;67:235–242 [CrossRef][PubMed]
    [Google Scholar]
  58. Vonrhein C, Blanc E, Roversi P, Bricogne G. Automated structure solution with autoSHARP. Methods Mol Biol 2007;364:215–230 [CrossRef][PubMed]
    [Google Scholar]
  59. Murshudov GN, Skubák P, Lebedev AA, Pannu NS, Steiner RA et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Cryst D 2011;67:355–367 [CrossRef][PubMed]
    [Google Scholar]
  60. Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Cryst D 2010;66:12–21 [CrossRef][PubMed]
    [Google Scholar]
  61. Krissinel E, Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol 2007;372:774–797 [CrossRef][PubMed]
    [Google Scholar]
  62. Holm L, Rosenström P. Dali server: conservation mapping in 3D. Nucleic Acids Res 2010;38:W545–W549 [CrossRef][PubMed]
    [Google Scholar]
  63. Wang L, Cummings RD, Smith DF, Huflejt M, Campbell CT et al. Cross-platform comparison of glycan microarray formats. Glycobiology 2014;24:507–517 [CrossRef][PubMed]
    [Google Scholar]
  64. Manimala JC, Roach TA, Li Z, Gildersleeve JC. High-throughput carbohydrate microarray profiling of 27 antibodies demonstrates widespread specificity problems. Glycobiology 2007;17:17C–23 [CrossRef][PubMed]
    [Google Scholar]
  65. Gounder AP, Myers ND, Treuting PM, Bromme BA, Wilson SS et al. Defensins potentiate a neutralizing antibody response to enteric viral infection. PLoS Pathog 2016;12:e1005474 [CrossRef][PubMed]
    [Google Scholar]
  66. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012;9:671–675 [CrossRef][PubMed]
    [Google Scholar]
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