1887

Abstract

Viruses pose a challenge to our imaginations. They exert a highly visible influence on the world in which we live, but operate at scales we cannot directly perceive and without a clear separation between their own biology and that of their hosts. Communication about viruses is therefore typically grounded in mental images of virus particles. Virus particles, as the infectious stage of the viral replication cycle, can be used to explain many directly observable properties of transmission, infection and immunity. In addition, their often striking beauty can stimulate further interest in virology. The structures of some virus particles have been determined experimentally in great detail, but for many important viruses a detailed description of the virus particle is lacking. This can be because they are challenging to describe with a single experimental method, or simply because of a lack of data. In these cases, methods from medical illustration can be applied to produce detailed visualisations of virus particles which integrate information from multiple sources. Here, we demonstrate how this approach was used to visualise the highly variable virus particles of influenza A viruses and, in the early months of the COVID-19 pandemic, the virus particles of the then newly characterised and poorly described SARS-CoV-2. We show how constructing integrative illustrations of virus particles can challenge our thinking about the biology of viruses, as well as providing tools for science communication, and we provide a set of science communication resources to help visualise two viruses whose effects are extremely apparent to all of us.

Funding
This study was supported by the:
  • Medical Research Council (Award [MR/N008618/1])
    • Principle Award Recipient: EdwardCharles Hutchinson
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
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2022-01-27
2024-03-28
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References

  1. Nee S, Smith JM. The evolutionary biology of molecular parasites. Parasitology 1990; 100 Suppl:S5–18 [View Article] [PubMed]
    [Google Scholar]
  2. Koonin EV, Dolja VV, Krupovic M, Kuhn JH. Viruses defined by the position of the virosphere within the replicator sDefined by the Position of the Virosphere within the Replicator Space. Microbiol Mol Biol Rev 2021; 85:e0019320 [View Article] [PubMed]
    [Google Scholar]
  3. Risco C, de Castro IF, Sanz-Sánchez L, Narayan K, Grandinetti G et al. Three-dimensional imaging of viral infections. Annu Rev Virol 2014; 1:453–473 [View Article] [PubMed]
    [Google Scholar]
  4. Ho PT, Montiel-Garcia DJ, Wong J, Carrillo-Tripp M, Brooks CL et al. VIPERdb: A tool for virus reseTool for Virus Research. Annu Rev Virol 2018; 5:477–488 [View Article]
    [Google Scholar]
  5. Twarock R, Luque A. Structural puzzles in virology solved with an overarching icosahedral design principle. Nat Commun 2019; 10:1–9 [View Article] [PubMed]
    [Google Scholar]
  6. Sali A. From integrative structural biology to cell biology. J Biol Chem 2021; 296:100743 [View Article]
    [Google Scholar]
  7. Rout MP, Sali A. Principles for integrative structural biology studies. Cell 2019; 177:1384–1403 [View Article] [PubMed]
    [Google Scholar]
  8. Kim SJ, Fernandez-Martinez J, Nudelman I, Shi Y, Zhang W et al. Integrative structure and functional anatomy of a nuclear pore complex. Nature 2018; 555:475–482 [View Article] [PubMed]
    [Google Scholar]
  9. Takamori S, Holt M, Stenius K, Lemke EA, Grønborg M et al. Molecular anatomy of a trafficking organelle. Cell 2006; 127:831–846 [View Article] [PubMed]
    [Google Scholar]
  10. Jimenez J, Autin L, De Cáceres II, Goodsell DS. Integrative modeling and visualization of exosomes. JBC 2019; 43: [View Article]
    [Google Scholar]
  11. Perilla JR, Hadden-Perilla JA, Gronenborn AM, Polenova T. Integrative structural biology of HIV-1 capsid protein assemblies: combining experiment and computation. Curr Opin Virol 2021; 48:57–64 [View Article] [PubMed]
    [Google Scholar]
  12. Nguyen N, Strnad O, Klein T, Luo D, Alharbi R et al. Modeling in the Time of COVID-19: statistical and rule-based mesoscale models. IEEE Trans Vis Comput Graph 2021; 27:722–732 [View Article] [PubMed]
    [Google Scholar]
  13. Yu A, Pak AJ, He P, Monje-Galvan V, Casalino L et al. A multiscale coarse-grained model of the SARS-CoV-2 virion. Biophys J 2021; 120:1097–1104 [View Article] [PubMed]
    [Google Scholar]
  14. Durrant JD, Kochanek SE, Casalino L, Ieong PU, Dommer AC et al. Mesoscale all-atom influenza virus simulations suggest new substrate binding mechanism. ACS Cent Sci 2020; 6:189–196 [View Article] [PubMed]
    [Google Scholar]
  15. Woolhouse M, Scott F, Hudson Z, Howey R, Chase-Topping M. Human viruses: discovery and emergence. Philos Trans R Soc Lond B Biol Sci 2012; 367:2864–2871 [View Article] [PubMed]
    [Google Scholar]
  16. Catanese MT, Uryu K, Kopp M, Edwards TJ, Andrus L et al. Ultrastructural analysis of hepatitis C virus particles. Proc Natl Acad Sci U S A 2013; 110:9505–9510 [View Article]
    [Google Scholar]
  17. Goodsell DS. Illustrating the machinery of life: Viruses. Biochem Mol Biol Educ 2012; 40:291–296 [View Article] [PubMed]
    [Google Scholar]
  18. Hutchinson EC, Yamauchi Y. Understanding influenza. Methods Mol Biol 2018; 1836:1–21 [View Article]
    [Google Scholar]
  19. Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 2018; 391:1285–1300 [View Article]
    [Google Scholar]
  20. Dochez AR, Mills KC, Kneeland Y. Studies of the etiology of influenza. Exp Biol Med 1933; 30:1017–1022 [View Article]
    [Google Scholar]
  21. Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. The Lancet 1933; 222:66–68 [View Article]
    [Google Scholar]
  22. Visual Science Influenza 3D model; 2021 https://www.visual-science.com/projects/influenza/3d-model/
  23. Reddy T, Shorthouse D, Parton DL, Jefferys E, Fowler PW et al. Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion. Structure 2015; 23:584–597 [View Article] [PubMed]
    [Google Scholar]
  24. Dadonaite B, Vijayakrishnan S, Fodor E, Bhella D, Hutchinson EC. Filamentous influenza viruses. J Gen Virol 2016; 97:1755–1764 [View Article] [PubMed]
    [Google Scholar]
  25. Hirst JC, Hutchinson EC. Single-particle measurements of filamentous influenza virions reveal damage induced by freezing. J Gen Virol 2019; 100:1631–1640 [View Article] [PubMed]
    [Google Scholar]
  26. Harris A, Cardone G, Winkler DC, Heymann JB, Brecher M et al. Influenza virus pleiomorphy characterized by cryoelectron tomography. Proc Natl Acad Sci U S A 2006; 103:19123–19127 [View Article] [PubMed]
    [Google Scholar]
  27. Tran EEH, Podolsky KA, Bartesaghi A, Kuybeda O, Grandinetti G et al. Cryo-electron microscopy structures of chimeric hemagglutinin displayed on a universal influenza vaccine candidate. mBio 2016; 7:e00257 [View Article] [PubMed]
    [Google Scholar]
  28. Calder LJ, Wasilewski S, Berriman JA, Rosenthal PB. Structural organization of a filamentous influenza A virus. Proc Natl Acad Sci U S A 2010; 107:10685–10690 [View Article] [PubMed]
    [Google Scholar]
  29. Wasilewski S, Calder LJ, Grant T, Rosenthal PB. Distribution of surface glycoproteins on influenza A virus determined by electron cryotomography. Vaccine 2012; 30:7368–7373 [View Article] [PubMed]
    [Google Scholar]
  30. Vijayakrishnan S, Loney C, Jackson D, Suphamungmee W, Rixon FJ et al. Cryotomography of budding influenza A virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end. PLoS Pathog 2013; 9:e1003413 [View Article] [PubMed]
    [Google Scholar]
  31. Hutchinson EC, Charles PD, Hester SS, Thomas B, Trudgian D et al. Conserved and host-specific features of influenza virion architecture. Nat Commun 2014; 5:4816 [View Article] [PubMed]
    [Google Scholar]
  32. Hutchinson EC, Stegmann M. Purification and proteomics of influenza virions. Methods Mol Biol 2018; 1836:89–120 [View Article] [PubMed]
    [Google Scholar]
  33. Xu D, Zhang Y. Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field. Proteins 2012; 80:1715–1735 [View Article] [PubMed]
    [Google Scholar]
  34. Xu D, Zhang Y. Toward optimal fragment generations for ab initio protein structure assembly. Proteins 2013; 81:229–239 [View Article] [PubMed]
    [Google Scholar]
  35. Tieleman DP, Berendsen HJCC. Molecular dynamics simulations of a fully hydrated dipalmitoylphosphatidylcholine bilayer with different macroscopic boundary conditions and parameters. The Journal of Chemical Physics 1996; 105:4871–4880 [View Article]
    [Google Scholar]
  36. Moeller A, Kirchdoerfer RN, Potter CS, Carragher B, Wilson IA. Organization of the influenza virus replication machinery. Science 2012; 338:1631–1634 [View Article] [PubMed]
    [Google Scholar]
  37. Arranz R, Coloma R, Chichón FJ, Conesa JJ, Carrascosa JL et al. The structure of native influenza virion ribonucleoproteins. Science 2012; 338:1634–1637 [View Article] [PubMed]
    [Google Scholar]
  38. Ortega J, Martín-Benito J, Zürcher T, Valpuesta JM, Carrascosa JL et al. Ultrastructural and functional analyses of recombinant influenza virus ribonucleoproteins suggest dimerization of nucleoprotein during virus amplification. J Virol 2000; 74:156–163 [View Article] [PubMed]
    [Google Scholar]
  39. Gallagher JR, Torian U, McCraw DM, Harris AK. Structural studies of influenza virus RNPs by electron microscopy indicate molecular contortions within NP supra-structures. J Struct Biol 2017; 197:294–307 [View Article] [PubMed]
    [Google Scholar]
  40. Noda T, Sagara H, Yen A, Takada A, Kida H et al. Architecture of ribonucleoprotein complexes in influenza A virus particles. Nature 2006; 439:490–492
    [Google Scholar]
  41. Noda T. Native morphology of influenza virions. Front Microbiol 2011; 2:269 [View Article]
    [Google Scholar]
  42. Noda T, Sugita Y, Aoyama K, Hirase A, Kawakami E et al. Three-dimensional analysis of ribonucleoprotein complexes in influenza A virus. Nat Commun 2012; 3:1–6 [View Article] [PubMed]
    [Google Scholar]
  43. Fournier E, Moules V, Essere B, Paillart J-C, Sirbat J-D et al. A supramolecular assembly formed by influenza A virus genomic RNA segments. Nucleic Acids Res 2012; 40:2197–2209 [View Article]
    [Google Scholar]
  44. Noda T, Kawaoka Y. Structure of influenza virus ribonucleoprotein complexes and their packaging into virions. Rev Med Virol 2010; 20:380–391 [View Article]
    [Google Scholar]
  45. Katz G, Benkarroum Y, Wei H, Rice WJ, Bucher D et al. Morphology of influenza B/Lee/40 determined by cryo-electron microscopy. PLoS One 2014; 9:e88288 [View Article] [PubMed]
    [Google Scholar]
  46. Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol 2006; 13:751–752 [View Article] [PubMed]
    [Google Scholar]
  47. Chang C, Hou M-H, Chang C-F, Hsiao C-D, Huang T. The SARS coronavirus nucleocapsid protein--forms and functions. Antiviral Res 2014; 103:39–50 [View Article] [PubMed]
    [Google Scholar]
  48. Neuman BW, Adair BD, Yoshioka C, Quispe JD, Orca G et al. Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy. J Virol 2006; 80:7918–7928 [View Article] [PubMed]
    [Google Scholar]
  49. Masters PS, Perlman S. In Fields BN, Knipe DN, Howley PM. eds Fields Virology Philadelphia: Lippincott Williams & Wilkins; 2013 pp 825–858
    [Google Scholar]
  50. Bárcena M, Oostergetel GT, Bartelink W, Faas FGA, Verkleij A et al. Cryo-electron tomography of mouse hepatitis virus: Insights into the structure of the coronavirion. Proc Natl Acad Sci U S A 2009; 106:582–587 [View Article] [PubMed]
    [Google Scholar]
  51. Surya W, Li Y, Torres J. Structural model of the SARS coronavirus E channel in LMPG micelles. Biochim Biophys Acta Biomembr 2018; 1860:1309–1317 [View Article] [PubMed]
    [Google Scholar]
  52. Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF et al. A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 2011; 174:11–22 [View Article] [PubMed]
    [Google Scholar]
  53. Jayaram H, Fan H, Bowman BR, Ooi A, Jayaram J et al. X-ray structures of the N- and C-terminal domains of a coronavirus nucleocapsid protein: implications for nucleocapsid formation. J Virol 2006; 80:6612–6620 [View Article] [PubMed]
    [Google Scholar]
  54. Zhang C, Zheng W, Huang X, Bell EW, Zhou X et al. Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1. J Proteome Res 2020; 19:1351–1360 [View Article] [PubMed]
    [Google Scholar]
  55. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181:281–292 [View Article] [PubMed]
    [Google Scholar]
  56. Frumkin R. How to Draw the Coronavirus. The Paris Review; 2020 https://www.theparisreview.org/blog/2020/05/18/how-to-draw-the-coronavirus/
  57. Casalino L, Gaieb Z, Goldsmith JA, Hjorth CK, Dommer AC et al. Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein. ACS Cent Sci 2020; 6:1722–1734 [View Article] [PubMed]
    [Google Scholar]
  58. Ke Z, Oton J, Qu K, Cortese M, Zila V et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature 2020; 588:498–502 [View Article] [PubMed]
    [Google Scholar]
  59. Yao H, Song Y, Chen Y, Wu N, Xu J et al. Molecular Architecture of the SARS-CoV-2 Virus. Cell 2020; 183:730–738 [View Article] [PubMed]
    [Google Scholar]
  60. Gardner A, Autin L, Fuentes D, Maritan M, Barad BA et al. CellPAINT: Turnkey Illustration of Molecular Cell Biology. Front Bioinform 2021; 1:7 [View Article] [PubMed]
    [Google Scholar]
  61. Goodsell DS, Voigt M, Zardecki C, Burley SK. Integrative illustration for coronavirus outreach. PLoS Biol 2020; 18:e3000815 [View Article] [PubMed]
    [Google Scholar]
  62. Falconieri Hays V. How I Built a 3-D Model of the Coronavirus for Scientific American; 2020 https://www.scientificamerican.com/article/how-i-built-a-3-d-model-of-the-coronavirus-for-scientific-american/
  63. Visual Science Coronavirus SARS-CoV-2: scientifically accurate 3D model le; 2020 https://visual-science.com/projects/sars-cov-2/3d-model/
  64. Nakano M, Sugita Y, Kodera N, Miyamoto S, Muramoto Y et al. Ultrastructure of influenza virus ribonucleoprotein complexes during viral RNA synthesis. Commun Biol 2021; 4:858 [View Article] [PubMed]
    [Google Scholar]
  65. Dommer A, Casalino L, Kearns F, Rosenfeld M, Wauer N et al. #COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy of Delta SARS-CoV-2 in a Respiratory Aerosol. bioRxiv 20212021.11.12.468428 [View Article]
    [Google Scholar]
  66. United Nations Environment Programme and International Livestock Research Institute Preventing the next pandemic: Zoonotic diseases and how to break the chain of transmission. Nairobi; 2020 https://hdl.handle.net/10568/108707
  67. Lakdawala SS, Nair N, Hutchinson E. Educational Material about Influenza Viruses. Viruses 2019; 11:E231 [View Article] [PubMed]
    [Google Scholar]
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