Editorial: Physical Virology and the Nature of Virus Infections

  • Urs F. GreberEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1215)


Virus particles, ‘virions’, range in size from nano-scale to micro-scale. They have many different shapes and are composed of proteins, sugars, nucleic acids, lipids, water and solutes. Virions are autonomous entities and affect all forms of life in a parasitic relationship. They infect prokaryotic and eukaryotic cells. The physical properties of virions are tuned to the way they interact with cells. When virions interact with cells, they gain huge complexity and give rise to an infected cell, also known as ‘virus’. Virion–cell interactions entail the processes of entry, replication and assembly, as well as egress from the infected cell. Collectively, these steps can result in progeny virions, which is a productive infection, or in silencing of the virus, an abortive or latent infection. This book explores facets of the physical nature of virions and viruses and the impact of mechanical properties on infection processes at the cellular and subcellular levels.


Physics Cell biology Virus Virion Computational virology Modelling Tracking Trafficking Uncoating Genome release Reverse transcription Structural evolution Viral lineage Active matter Liquid unmixing Inclusion bodies Virion morphogenesis Maturation Mechanical properties Stiffness Pressure Water wire Acidic pH Alkaline pH Proton diode Anisotropic mechanics 



I would like to thank all the authors for their valuable contributions, the reviewers of the chapters for insightful and constructive comments and Maarit Suomalainen for comments to the editorial text.


  1. 1.
    Beadle GW, Tatum EL (1941) Genetic control of biochemical reactions in Neurospora. Proc Natl Acad Sci U S A 27:499–506. PubMedPubMedCentralGoogle Scholar
  2. 2.
    Dronamraju KR (1999) Erwin Schrodinger and the origins of molecular biology. Genetics 153:1071–1076PubMedPubMedCentralGoogle Scholar
  3. 3.
    Luria SE, Delbruck M (1943) Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491–511PubMedPubMedCentralGoogle Scholar
  4. 4.
    Nedelec FJ, Surrey T, Maggs AC, Leibler S (1997) Self-organization of microtubules and motors. Nature 389:305–308. PubMedGoogle Scholar
  5. 5.
    Toner J, Tu Y (1995) Long-range order in a two-dimensional dynamical XY model: how birds fly together. Phys Rev Lett 75:4326–4329. PubMedGoogle Scholar
  6. 6.
    Vicsek T, Czirok A, Ben-Jacob E, Cohen II, Shochet O (1995) Novel type of phase transition in a system of self-driven particles. Phys Rev Lett 75:1226–1229. PubMedGoogle Scholar
  7. 7.
    Caspar DL, Klug A (1962) Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol 27:1–24. PubMedGoogle Scholar
  8. 8.
    Johnson JE, Speir JA (1997) Quasi-equivalent viruses: a paradigm for protein assemblies. J Mol Biol 269:665–675. PubMedGoogle Scholar
  9. 9.
    Domingo E, Sabo D, Taniguchi T, Weissmann C (1978) Nucleotide sequence heterogeneity of an RNA phage population. Cell 13:735–744. PubMedPubMedCentralGoogle Scholar
  10. 10.
    Eigen M (1993) Viral quasispecies. Sci Am 269:42–49PubMedGoogle Scholar
  11. 11.
    Greber UF, Bartenschlager R (2017) An expanded view of viruses. FEMS Microbiol Rev 41:1–4. PubMedGoogle Scholar
  12. 12.
    Lederberg J (2000) Infectious history. Science 288:287–293. PubMedGoogle Scholar
  13. 13.
    Cisek AA, Dabrowska I, Gregorczyk KP, Wyzewski Z (2017) Phage therapy in bacterial infections treatment: one hundred years after the discovery of bacteriophages. Curr Microbiol 74:277–283. PubMedGoogle Scholar
  14. 14.
    Schmid M, Ernst P, Honegger A, Suomalainen M, Zimmermann M, Braun L, Stauffer S, Thom C, Dreier B, Eibauer M et al (2018) Adenoviral vector with shield and adapter increases tumor specificity and escapes liver and immune control. Nat Commun 9:450. PubMedPubMedCentralGoogle Scholar
  15. 15.
    Young R, Gill JJ (2015) Microbiology. Phage therapy redux – what is to be done? Science 350:1163–1164. PubMedPubMedCentralGoogle Scholar
  16. 16.
    Nathan L, Daniel S (2019) Single virion tracking microscopy for the study of virus entry processes in live cells and biomimetic platforms. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  17. 17.
    Rodríguez JM, Luque D (2019) Structural insights into rotavirus entry. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  18. 18.
    James LC (2019) The HIV-1 capsid: more than just a delivery package. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  19. 19.
    Fay N, Pante N (2015) Old foes, new understandings: nuclear entry of small non-enveloped DNA viruses. Curr Opin Virol 12:59–65. PubMedGoogle Scholar
  20. 20.
    Flatt JW, Greber UF (2017) Viral mechanisms for docking and delivering at nuclear pore complexes. Semin Cell Dev Biol 68:59–71. PubMedGoogle Scholar
  21. 21.
    Radtke K, Dohner K, Sodeik B (2006) Viral interactions with the cytoskeleton: a Hitchhiker’s guide to the cell. Cell Microbiol 8:387–400. PubMedGoogle Scholar
  22. 22.
    Wang IH, Burckhardt CJ, Yakimovich A, Greber UF (2018) Imaging, tracking and computational analyses of virus entry and egress with the cytoskeleton. Viruses 10(4):166. PubMedCentralGoogle Scholar
  23. 23.
    Yamauchi Y, Greber UF (2016) Principles of virus uncoating: cues and the snooker ball. Traffic 17:569–592. PubMedPubMedCentralGoogle Scholar
  24. 24.
    Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC (2016) HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Nature 536:349–353. PubMedPubMedCentralGoogle Scholar
  25. 25.
    Tanaka S, Sawaya MR, Yeates TO (2010) Structure and mechanisms of a protein-based organelle in Escherichia coli. Science 327:81–84. Google Scholar
  26. 26.
    Chowdhury C, Chun S, Pang A, Sawaya MR, Sinha S, Yeates TO, Bobik TA (2015) Selective molecular transport through the protein shell of a bacterial microcompartment organelle. Proc Natl Acad Sci U S A 112:2990–2995. PubMedPubMedCentralGoogle Scholar
  27. 27.
    Oksanen HM, Abrescia NGA (2019) Membrane-containing Icosahedral Bacteriophage PRD1: the dawn of viral lineages. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  28. 28.
    Espejo RT, Canelo ES (1968) Properties of bacteriophage PM2: a lipid-containing bacterial virus. Virology 34:738–747. PubMedGoogle Scholar
  29. 29.
    Bamford DH, Burnett RM, Stuart DI (2002) Evolution of viral structure. Theor Popul Biol 61:461–470. PubMedGoogle Scholar
  30. 30.
    Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht HJ, Johnson JE, Kamer G, Luo M, Mosser AG et al (1985) Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317:145–153. PubMedGoogle Scholar
  31. 31.
    Roulin PS, Lotzerich M, Torta F, Tanner LB, van Kuppeveld FJ, Wenk MR, Greber UF (2014) Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface. Cell Host Microbe 16:677–690. PubMedGoogle Scholar
  32. 32.
    Benson SD, Bamford JK, Bamford DH, Burnett RM (1999) Viral evolution revealed by bacteriophage PRD1 and human adenovirus coat protein structures. Cell 98:825–833. PubMedGoogle Scholar
  33. 33.
    Stromsten NJ, Bamford DH, Bamford JK (2003) The unique vertex of bacterial virus PRD1 is connected to the viral internal membrane. J Virol 77:6314–6321. PubMedPubMedCentralGoogle Scholar
  34. 34.
    Liu H, Jin L, Koh SB, Atanasov I, Schein S, Wu L, Zhou ZH (2010) Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science 329:1038–1043. PubMedPubMedCentralGoogle Scholar
  35. 35.
    Yu X, Veesler D, Campbell MG, Barry ME, Asturias FJ, Barry MA, Reddy VS (2017) Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses. Sci Adv 3:e1602670. PubMedPubMedCentralGoogle Scholar
  36. 36.
    Cardone G, Winkler DC, Trus BL, Cheng N, Heuser JE, Newcomb WW, Brown JC, Steven AC (2007) Visualization of the herpes simplex virus portal in situ by cryo-electron tomography. Virology 361:426–434. PubMedGoogle Scholar
  37. 37.
    Condezo GN, San Martin C (2017) Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center. PLoS Pathog 13:e1006320. PubMedPubMedCentralGoogle Scholar
  38. 38.
    Ostapchuk P, Suomalainen M, Zheng Y, Boucke K, Greber UF, Hearing P (2017) The adenovirus major core protein VII is dispensable for virion assembly but is essential for lytic infection. PLoS Pathog 13:e1006455. PubMedPubMedCentralGoogle Scholar
  39. 39.
    Nikolic J, Lagaudrière-Gesbert C, Scrima N, Blondel D, Gaudin Y (2019) Structure and function of Negri bodies. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  40. 40.
    San Martín C (2019) Virus maturation. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  41. 41.
    Greber UF, Singh I, Helenius A (1994) Mechanisms of virus uncoating. Trends Microbiol 2:52–56. PubMedGoogle Scholar
  42. 42.
    Imelli N, Ruzsics Z, Puntener D, Gastaldelli M, Greber UF (2009) Genetic reconstitution of the human adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape. Virol J 6:174. PubMedPubMedCentralGoogle Scholar
  43. 43.
    Kilcher S, Mercer J (2015) DNA virus uncoating. Virology 479–480:578–590. PubMedGoogle Scholar
  44. 44.
    Suomalainen M, Greber UF (2013) Uncoating of non-enveloped viruses. Curr Opin Virol 3:27–33. PubMedPubMedCentralGoogle Scholar
  45. 45.
    Evilevitch A, Roos WH, Ivanovska IL, Jeembaeva M, Jonsson B, Wuite GJ (2011) Effects of salts on internal DNA pressure and mechanical properties of phage capsids. J Mol Biol 405:18–23. PubMedGoogle Scholar
  46. 46.
    Klug WS, Roos WH, Wuite GJ (2012) Unlocking internal prestress from protein nanoshells. Phys Rev Lett 109:168104. PubMedGoogle Scholar
  47. 47.
    Greber UF (2014) How cells tune viral mechanics – insights from biophysical measurements of influenza virus. Biophys J 106:2317–2321. PubMedPubMedCentralGoogle Scholar
  48. 48.
    Li S, Sieben C, Ludwig K, Hofer CT, Chiantia S, Herrmann A, Eghiaian F, Schaap IA (2014) pH-controlled two-step uncoating of influenza virus. Biophys J 106:1447–1456. PubMedPubMedCentralGoogle Scholar
  49. 49.
    de Pablo PJ, Schaap IAT (2019) Atomic force microscopy of viruses. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  50. 50.
    Pang HB, Hevroni L, Kol N, Eckert DM, Tsvitov M, Kay MS, Rousso I (2013) Virion stiffness regulates immature HIV-1 entry. Retrovirology 10:4. PubMedPubMedCentralGoogle Scholar
  51. 51.
    Burckhardt CJ, Greber UF (2009) Virus movements on the plasma membrane support infection and transmission between cells. PLoS Pathog 5:e1000621. PubMedPubMedCentralGoogle Scholar
  52. 52.
    Burckhardt CJ, Suomalainen M, Schoenenberger P, Boucke K, Hemmi S, Greber UF (2011) Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure. Cell Host Microbe 10:105–117. PubMedGoogle Scholar
  53. 53.
    Strunze S, Engelke MF, Wang IH, Puntener D, Boucke K, Schleich S, Way M, Schoenenberger P, Burckhardt CJ, Greber UF (2011) Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection. Cell Host Microbe 10:210–223. PubMedGoogle Scholar
  54. 54.
    Bauer DW, Huffman JB, Homa FL, Evilevitch A (2013) Herpes virus genome, the pressure is on. J Am Chem Soc 135:11216–11221. PubMedPubMedCentralGoogle Scholar
  55. 55.
    Greber UF (2016) Virus and host mechanics support membrane penetration and cell entry. J Virol 90:3802–3805. PubMedPubMedCentralGoogle Scholar
  56. 56.
    Luisoni S, Greber UF (2016) Biology of adenovirus cell entry – receptors, pathways, mechanisms. In: Curiel D (ed) Adenoviral vectors for gene therapy. Academic Press, London, pp 27–58. ISBN: 9780128002766Google Scholar
  57. 57.
    Hernando-Perez M, Miranda R, Aznar M, Carrascosa JL, Schaap IA, Reguera D, de Pablo PJ (2012) Direct measurement of phage phi29 stiffness provides evidence of internal pressure. Small 8:2366–2370. Google Scholar
  58. 58.
    Branda MM, Guérin DMA (2019) Alkalinization of Icosahedral nonenveloped viral capsid interior through proton channeling. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  59. 59.
    Martin-Gonzalez N, Guerin Darvas SM, Durana A, Marti GA, Guerin DMA, de Pablo PJ (2018) Exploring the role of genome and structural ions in preventing viral capsid collapse during dehydration. J Phys Condens Matter 30:104001. PubMedGoogle Scholar
  60. 60.
    Greber UF, Willetts M, Webster P, Helenius A (1993) Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75:477–486. Google Scholar
  61. 61.
    Nakano MY, Boucke K, Suomalainen M, Stidwill RP, Greber UF (2000) The first step of adenovirus type 2 disassembly occurs at the cell surface, independently of endocytosis and escape to the cytosol. J Virol 74:7085–7095. PubMedPubMedCentralGoogle Scholar
  62. 62.
    Ortega-Esteban A, Bodensiek K, San Martin C, Suomalainen M, Greber UF, de Pablo PJ, Schaap IA (2015) Fluorescence tracking of genome release during mechanical unpacking of single viruses. ACS Nano 9:10571–10579. Google Scholar
  63. 63.
    Snijder J, Reddy VS, May ER, Roos WH, Nemerow GR, Wuite GJ (2013) Integrin and defensin modulate the mechanical properties of adenovirus. J Virol 87:2756–2766. PubMedPubMedCentralGoogle Scholar
  64. 64.
    Wang IH, Suomalainen M, Andriasyan V, Kilcher S, Mercer J, Neef A, Luedtke NW, Greber UF (2013) Tracking viral genomes in host cells at single-molecule resolution. Cell Host Microbe 14:468–480. PubMedGoogle Scholar
  65. 65.
    Jefferys EE, Sansom MPS (2019) Computational virology: molecular simulations of virus dynamics and interactions. In: Greber UF (ed) Physical virology – virus structure and mechanics. Springer, BerlinGoogle Scholar
  66. 66.
    Sbalzarini IF, Greber UF (2018) How computational models enable mechanistic insights into virus infection. Methods Mol Biol 1836:609–631. PubMedGoogle Scholar
  67. 67.
    Witte R, Andriasyan V, Georgi F, Yakimovich A, Greber UF (2018) Concepts in light microscopy of viruses. Viruses 10(4):202. PubMedCentralGoogle Scholar
  68. 68.
    Summers WC (1993) How bacteriophage came to be used by the Phage Group. J Hist Biol 26:255–267. PubMedGoogle Scholar
  69. 69.
    Evilevitch A (2013) Physical evolution of pressure-driven viral infection. Biophys J 104:2113–2114. PubMedPubMedCentralGoogle Scholar
  70. 70.
    Yin J, Redovich J (2018) Kinetic modeling of virus growth in cells. Microbiol Mol Biol Rev 82:e00066–00017. Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Molecular Life SciencesUniversity of ZurichZurichSwitzerland

Personalised recommendations