1932

Abstract

Phase separation of viral biopolymers is a key factor in the formation of cytoplasmic viral inclusions, known as sites of virus replication and assembly. This review describes the mechanisms and factors that affect phase separation in viral replication and identifies potential areas for future research. Drawing inspiration from studies on cellular RNA-rich condensates, we compare the hierarchical coassembly of ribosomal RNAs and proteins in the nucleolus to the coordinated coassembly of viral RNAs and proteins taking place within viral factories in viruses containing segmented RNA genomes. We highlight the common characteristics of biomolecular condensates in viral replication and how this new understanding is reshaping our views of virus assembly mechanisms. Such studies have the potential to uncover unexplored antiviral strategies targeting these phase-separated states.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-virology-111821-103226
2023-09-29
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/virology/10/1/annurev-virology-111821-103226.html?itemId=/content/journals/10.1146/annurev-virology-111821-103226&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Zlotnick A. 2003. Are weak protein–protein interactions the general rule in capsid assembly?. Virology 315:2269–74
    [Google Scholar]
  2. 2.
    Stockley PG, Twarock R, Bakker SE, Barker AM, Borodavka A et al. 2013. Packaging signals in single-stranded RNA viruses: nature's alternative to a purely electrostatic assembly mechanism. J. Biol. Phys. 39:2277–87
    [Google Scholar]
  3. 3.
    Borodavka A, Tuma R, Stockley PG. 2012. Evidence that viral RNAs have evolved for efficient, two-stage packaging. PNAS 109:3915769–74
    [Google Scholar]
  4. 4.
    den Boon JA, Ahlquist P. 2010. Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories. Annu. Rev. Microbiol. 64:241–56
    [Google Scholar]
  5. 5.
    de Castro IF, Volonté L, Risco C. 2013. Virus factories: biogenesis and structural design. Cell. Microbiol. 15:124–34
    [Google Scholar]
  6. 6.
    Risco C, de Castro IF, Sanz-Sánchez L, Narayan K, Grandinetti G, Subramaniam S. 2014. Three-dimensional imaging of viral infections. Annu. Rev. Virol. 1:453–73
    [Google Scholar]
  7. 7.
    Netherton CL, Wileman T. 2011. Virus factories, double membrane vesicles and viroplasm generated in animal cells. Curr. Opin. Virol. 1:5381–87
    [Google Scholar]
  8. 8.
    Nikolic J, Le Bars R, Lama Z, Scrima N, Lagaudrière-Gesbert C et al. 2017. Negri bodies are viral factories with properties of liquid organelles. Nat. Commun. 8:158
    [Google Scholar]
  9. 9.
    Shaw MW, Compans RW. 1978. Isolation and characterization of cytoplasmic inclusions from influenza A virus-infected cells. J. Virol. 25:2608–15
    [Google Scholar]
  10. 10.
    Howard AR, Moss B. 2012. Formation of orthopoxvirus cytoplasmic A-type inclusion bodies and embedding of virions are dynamic processes requiring microtubules. J. Virol. 86:105905–14
    [Google Scholar]
  11. 11.
    Smith KM 1958. Virus inclusions in plant cells. The Multiplication of Viruses SE Luria, KM Smith, P Fredericq 65–80. Vienna: Springer Vienna
    [Google Scholar]
  12. 12.
    Brangwynne CP, Eckmann CR, Courson DS, Rybarska A, Hoege C et al. 2009. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324:59351729–32
    [Google Scholar]
  13. 13.
    Banani SF, Lee HO, Hyman AA, Rosen MK. 2017. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18:5285–98
    [Google Scholar]
  14. 14.
    Brangwynne CP, Tompa P, Pappu RV. 2015. Polymer physics of intracellular phase transitions. Nat. Phys. 11:11899–904
    [Google Scholar]
  15. 15.
    Shin Y, Brangwynne CP. 2017. Liquid phase condensation in cell physiology and disease. Science 357:6357eaaf4382
    [Google Scholar]
  16. 16.
    Langdon EM, Gladfelter AS. 2018. A new lens for RNA localization: liquid-liquid phase separation. Annu. Rev. Microbiol. 72:255–71
    [Google Scholar]
  17. 17.
    Alberti S, Gladfelter A, Mittag T. 2019. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell 176:3419–34
    [Google Scholar]
  18. 18.
    Choi J-M, Holehouse AS, Pappu RV. 2020. Physical principles underlying the complex biology of intracellular phase transitions. Annu. Rev. Biophys. 49:107–33
    [Google Scholar]
  19. 19.
    Mittag T, Pappu RV. 2022. A conceptual framework for understanding phase separation and addressing open questions and challenges. Mol. Cell 82:122201–14
    [Google Scholar]
  20. 20.
    Lopez N, Camporeale G, Salgueiro M, Borkosky SS, Visentín A et al. 2021. Deconstructing virus condensation. PLOS Pathog. 17:10e1009926
    [Google Scholar]
  21. 21.
    Wu C, Holehouse AS, Leung DW, Amarasinghe GK, Dutch RE. 2022. Liquid phase partitioning in virus replication: observations and opportunities. Annu. Rev. Virol. 9:285–306
    [Google Scholar]
  22. 22.
    Li H, Ernst C, Kolonko-Adamska M, Greb-Markiewicz B, Man J et al. 2022. Phase separation in viral infections. Trends Microbiol. 30:121217–31
    [Google Scholar]
  23. 23.
    Heinrich BS, Maliga Z, Stein DA, Hyman AA, Whelan SPJ. 2018. Phase transitions drive the formation of vesicular stomatitis virus replication compartments. mBio 9:5e02290–17
    [Google Scholar]
  24. 24.
    Milles S, Jensen MR, Lazert C, Guseva S, Ivashchenko S et al. 2018. An ultraweak interaction in the intrinsically disordered replication machinery is essential for measles virus function. Sci. Adv. 4:8eaat7778
    [Google Scholar]
  25. 25.
    Guseva S, Milles S, Jensen MR, Salvi N, Kleman JP et al. 2020. Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly. Sci. Adv. 6:14eaaz7095
    [Google Scholar]
  26. 26.
    Alenquer M, Vale-Costa S, Etibor TA, Ferreira F, Sousa AL, Amorim MJ. 2019. Influenza A virus ribonucleoproteins form liquid organelles at endoplasmic reticulum exit sites. Nat. Commun. 10:11629
    [Google Scholar]
  27. 27.
    Geiger F, Acker J, Papa G, Wang X, Arter WE et al. 2021. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. EMBO J. 40:21e107711
    [Google Scholar]
  28. 28.
    Iserman C, Roden CA, Boerneke MA, Sealfon RSG, McLaughlin GA et al. 2020. Genomic RNA elements drive phase separation of the SARS-CoV-2 nucleocapsid. Mol. Cell 80:61078–91.e6
    [Google Scholar]
  29. 29.
    Savastano A, Ibáñez de Opakua A, Rankovic M, Zweckstetter M. 2020. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nat. Commun. 11:16041
    [Google Scholar]
  30. 30.
    Tsai WC, Lloyd RE. 2014. Cytoplasmic RNA granules and viral infection. Annu. Rev. Virol. 1:147–70
    [Google Scholar]
  31. 31.
    Alberti S. 2017. Phase separation in biology. Curr. Biol. 27:20R1097–102
    [Google Scholar]
  32. 32.
    Wei MT, Elbaum-Garfinkle S, Holehouse AS, Chen CCH, Feric M et al. 2017. Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. Nat. Chem. 9:111118–25
    [Google Scholar]
  33. 33.
    Nott TJ, Craggs TD, Baldwin AJ. 2016. Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters. Nat. Chem. 8:6569–75
    [Google Scholar]
  34. 34.
    Rhine K, Vidaurre V, Myong S 2020. RNA droplets. Annu. Rev. Biophys. 49:247–65
    [Google Scholar]
  35. 35.
    King DS, Jiang Q-X, Kim S, Nixon BT, Guo L et al. 2012. Phase transitions in the assembly of multivalent signalling proteins. Nature 483:7389336–40
    [Google Scholar]
  36. 36.
    Zwicker D, Hyman AA, Jülicher F. 2015. Suppression of Ostwald ripening in active emulsions. Phys. Rev. E 92:112317
    [Google Scholar]
  37. 37.
    Dar F, Pappu R. 2020. Restricting the sizes of condensates. eLife 9:e59663
    [Google Scholar]
  38. 38.
    Ma W, Mayr C. 2018. A membraneless organelle associated with the endoplasmic reticulum enables 3′UTR-mediated protein-protein interactions. Cell 175:61492–506.e19
    [Google Scholar]
  39. 39.
    Dignon GL, Best RB, Mittal J. 2020. Biomolecular phase separation: from molecular driving forces to macroscopic properties. Annu. Rev. Phys. Chem. 71:53–75
    [Google Scholar]
  40. 40.
    Swain P, Weber SC. 2020. Dissecting the complexity of biomolecular condensates. Biochem. Soc. Trans. 48:62591–602
    [Google Scholar]
  41. 41.
    Hastings RL, Boeynaems S. 2021. Designer condensates: a toolkit for the biomolecular architect. J. Mol. Biol. 433:12166837
    [Google Scholar]
  42. 42.
    Peran I, Mittag T. 2019. Molecular structure in biomolecular condensates. Curr. Opin. Struct. Biol. 60:17–26
    [Google Scholar]
  43. 43.
    Papa G, Borodavka A, Desselberger U. 2021. Viroplasms: assembly and functions of rotavirus replication factories. Viruses 13:71349
    [Google Scholar]
  44. 44.
    Bah A, Forman-Kay JD. 2016. Modulation of intrinsically disordered protein function by post-translational modifications. J. Biol. Chem. 291:136696–705
    [Google Scholar]
  45. 45.
    Hofweber M, Dormann D. 2019. Friend or foe—post-translational modifications as regulators of phase separation and RNP granule dynamics. J. Biol. Chem. 294:187137–50
    [Google Scholar]
  46. 46.
    Monahan Z, Ryan VH, Janke AM, Burke KA, Rhoads SN et al. 2017. Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity. EMBO J. 36:202951–67
    [Google Scholar]
  47. 47.
    Tsang B, Arsenault J, Vernon RM, Lin H, Sonenberg N et al. 2019. Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation. PNAS 116:104218–27
    [Google Scholar]
  48. 48.
    Aumiller WM, Keating CD. 2016. Phosphorylation-mediated RNA/peptide complex coacervation as a model for intracellular liquid organelles. Nat. Chem. 8:2129–37
    [Google Scholar]
  49. 49.
    Wang A, Conicella AE, Schmidt HB, Martin EW, Rhoads SN et al. 2018. A single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing. EMBO J. 37:5e97452
    [Google Scholar]
  50. 50.
    Saito M, Hess D, Eglinger J, Fritsch AW, Kreysing M et al. 2019. Acetylation of intrinsically disordered regions regulates phase separation. Nat. Chem. Biol. 15:151–61
    [Google Scholar]
  51. 51.
    Hofweber M, Hutten S, Bourgeois B, Spreitzer E, Niedner-Boblenz A et al. 2018. Phase separation of FUS is suppressed by its nuclear import receptor and arginine methylation. Cell 173:3706–19.e13
    [Google Scholar]
  52. 52.
    Conicella AE, Zerze GH, Mittal J, Fawzi NL. 2016. ALS mutations disrupt phase separation mediated by α-helical structure in the TDP-43 low-complexity C-terminal domain. Structure 24:91537–49
    [Google Scholar]
  53. 53.
    Papa G, Venditti L, Arnoldi F, Schraner EM, Potgieter C et al. 2020. Recombinant rotaviruses rescued by reverse genetics reveal the role of NSP5 hyperphosphorylation in the assembly of viral factories. J. Virol. 94:1e01110–19
    [Google Scholar]
  54. 54.
    Wang J, Choi J, Holehouse AS, Lee HO, Zhang X et al. 2018. A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174:3688–99
    [Google Scholar]
  55. 55.
    Saar KL, Morgunov AS, Qi R, Arter WE, Krainer G et al. 2021. Learning the molecular grammar of protein condensates from sequence determinants and embeddings. PNAS 118:15e2019053118
    [Google Scholar]
  56. 56.
    Kroschwald S, Maharana S, Alberti S. 2017. Hexanediol: a chemical probe to investigate the material properties of membrane-less compartments. Matters 3:e201702000010
    [Google Scholar]
  57. 57.
    Krainer G, Welsh TJ, Joseph JA, Espinosa JR, Wittmann S et al. 2021. Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions. Nat. Commun. 12:11085
    [Google Scholar]
  58. 58.
    Strauss S, Acker J, Papa G, Desiró D, Schueder F et al. 2023. Principles of RNA recruitment to viral ribonucleoprotein condensates in a segmented dsRNA virus. eLife 12:e68670
    [Google Scholar]
  59. 59.
    Feric M, Vaidya N, Harmon TS, Mitrea DM, Zhu L et al. 2016. Coexisting liquid phases underlie nucleolar subcompartments. Cell 165:71686–97
    [Google Scholar]
  60. 60.
    Alberts B. 2022. Molecular Biology of the Cell New York: W.W. Norton., 7th ed..
  61. 61.
    Wheeler JR, Matheny T, Jain S, Abrisch R, Parker R. 2016. Distinct stages in stress granule assembly and disassembly. eLife 5:e18413
    [Google Scholar]
  62. 62.
    Freibaum BD, Messing J, Yang P, Kim HJ, Taylor JP. 2021. High-fidelity reconstitution of stress granules and nucleoli in mammalian cellular lysate. J. Cell Biol. 220:3e202009079
    [Google Scholar]
  63. 63.
    Borodavka A, Singaram SW, Stockley PG, Gelbart WM, Ben-Shaul A, Tuma R. 2016. Sizes of long RNA molecules are determined by the branching patterns of their secondary structures. Biophys. J. 111:102077–85
    [Google Scholar]
  64. 64.
    Ma W, Zheng G, Xie W, Mayr C. 2021. In vivo reconstitution finds multivalent RNA–RNA interactions as drivers of mesh-like condensates. eLife 10:e64252
    [Google Scholar]
  65. 65.
    Langdon EM, Qiu Y, Niaki AG, McLaughlin GA, Weidmann CA et al. 2018. mRNA structure determines specificity of a polyQ-driven phase separation. Science 360:6391922–27
    [Google Scholar]
  66. 66.
    Banerjee PR, Milin AN, Moosa MM, Onuchic PL, Deniz AA. 2017. Reentrant phase transition drives dynamic substructure formation in ribonucleoprotein droplets. Angew. Chem. Int. Ed. 56:3811354–59
    [Google Scholar]
  67. 67.
    Sanders DW, Kedersha N, Lee DSW, Strom AR, Drake V et al. 2020. Competing protein-RNA interaction networks control multiphase intracellular organization. Cell 181:2306–24.e28
    [Google Scholar]
  68. 68.
    Yamazaki T, Souquere S, Chujo T, Kobelke S, Chong YS et al. 2018. Functional domains of NEAT1 architectural lncRNA induce paraspeckle assembly through phase separation. Mol. Cell 70:61038–53.e7
    [Google Scholar]
  69. 69.
    Portz B, Shorter J. 2021. Biochemical timekeeping via reentrant phase transitions. J. Mol. Biol. 433:12166794
    [Google Scholar]
  70. 70.
    Kaur T, Raju M, Alshareedah I, Davis RB, Potoyan DA, Banerjee PR. 2021. Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies. Nat. Commun. 12:1872
    [Google Scholar]
  71. 71.
    Desmet EA, Anguish LJ, Parker JS. 2014. Virus-mediated compartmentalization of the host translational machinery. mBio 5:5e01463–14
    [Google Scholar]
  72. 72.
    Caddy S, Papa G, Borodavka A, Desselberger U. 2021. Rotavirus research: 2014–2020. Virus Res. 304:198499
    [Google Scholar]
  73. 73.
    Eichwald C, Rodriguez JF, Burrone OR. 2004. Characterization of rotavirus NSP2/NSP5 interactions and the dynamics of viroplasm formation. J. Gen. Virol. 85:3625–34
    [Google Scholar]
  74. 74.
    Contin R, Arnoldi F, Campagna M, Burrone OR. 2010. Rotavirus NSP5 orchestrates recruitment of viroplasmic proteins. J. Gen. Virol. 91:1782–93
    [Google Scholar]
  75. 75.
    Criglar JM, Hu L, Crawford SE, Hyser JM, Broughman JR et al. 2014. A novel form of rotavirus NSP2 and phosphorylation-dependent NSP2-NSP5 interactions are associated with viroplasm assembly. J. Virol. 88:2786–98
    [Google Scholar]
  76. 76.
    Criglar JM, Anish R, Hu L, Crawford SE, Sankaran B et al. 2018. Phosphorylation cascade regulates the formation and maturation of rotaviral replication factories. PNAS 115:51E12015–23
    [Google Scholar]
  77. 77.
    Buttafuoco A, Michaelsen K, Tobler K. 2020. Conserved rotavirus NSP5 and VP2 domains interact and affect viroplasm. J. Virol. 94:7e01965–19
    [Google Scholar]
  78. 78.
    Nichols SL, Nilsson E, Brown-Harding H, LaConte LE, Acker J et al. 2023. Flexibility of the rotavirus NSP2 C-terminal region supports factory formation via liquid-liquid phase separation. J. Virol. 2023:e00039–23
    [Google Scholar]
  79. 79.
    Arnoldi F, Campagna M, Eichwald C, Desselberger U, Burrone OR. 2007. Interaction of rotavirus polymerase VP1 with nonstructural protein NSP5 is stronger than that with NSP2. J. Virol. 81:52128–37
    [Google Scholar]
  80. 80.
    Garcés Suárez Y, Martínez JL, Torres Hernández D, Hernández HO, Pérez-Delgado A et al. 2019. Nanoscale organization of rotavirus replication machineries. eLife 8:e42906
    [Google Scholar]
  81. 81.
    Fare CM, Villani A, Drake LE, Shorter J. 2021. Higher-order organization of biomolecular condensates. Open Biol. 11:6210137
    [Google Scholar]
  82. 82.
    Linsenmeier M, Hondele M, Grigolato F, Secchi E, Weis K, Arosio P. 2022. Dynamic arrest and aging of biomolecular condensates are modulated by low-complexity domains, RNA and biochemical activity. Nat. Commun. 13:13030
    [Google Scholar]
  83. 83.
    Miller CL, Broering TJ, Parker JSL, Arnold MM, Nibert ML. 2003. Reovirus σNS protein localizes to inclusions through an association requiring the μNS amino terminus. J. Virol. 77:84566–76
    [Google Scholar]
  84. 84.
    Forman-Kay JD, Ditlev JA, Nosella ML, Lee HO. 2022. What are the distinguishing features and size requirements of biomolecular condensates and their implications for RNA-containing condensates?. RNA 28:136–47
    [Google Scholar]
  85. 85.
    Rahman SK, Ampah KK, Roy P. 2022. Role of NS2 specific RNA binding and phosphorylation in liquid–liquid phase separation and virus assembly. Nucleic Acids Res. 50:1911273–84
    [Google Scholar]
  86. 86.
    Campbell EA, Reddy VRAP, Gray AG, Wells J, Simpson J et al. 2020. Discrete virus factories form in the cytoplasm of cells coinfected with two replication-competent tagged reporter birnaviruses that subsequently coalesce over time. J. Virol. 94:13e02107–19
    [Google Scholar]
  87. 87.
    Bussiere LD, Choudhury P, Bellaire B, Miller CL. 2017. Characterization of a replicating mammalian orthoreovirus with tetracysteine-tagged μNS for live-cell visualization of viral factories. J. Virol. 91:22e01371–17
    [Google Scholar]
  88. 88.
    Guo Y, Parker JSL. 2021. The paradoxes of viral mRNA translation during mammalian orthoreovirus infection. Viruses 13:2275
    [Google Scholar]
  89. 89.
    McDonald SM, Nelson MI, Turner PE, Patton JT. 2016. Reassortment in segmented RNA viruses: mechanisms and outcomes. Nat. Rev. Microbiol. 14:7448–60
    [Google Scholar]
  90. 90.
    Borodavka A, Dykeman EC, Schrimpf W, Lamb DC. 2017. Protein-mediated RNA folding governs sequence-specific interactions between rotavirus genome segments. eLife 6:e27453
    [Google Scholar]
  91. 91.
    Bravo JPK, Borodavka A, Barth A, Calabrese AN, Mojzes P et al. 2018. Stability of local secondary structure determines selectivity of viral RNA chaperones. Nucleic Acids Res. 46:157924–37
    [Google Scholar]
  92. 92.
    Coria A, Wienecke A, Knight ML, Desirò D, Laederach A, Borodavka A. 2022. Rotavirus RNA chaperone mediates global transcriptome-wide increase in RNA backbone flexibility. Nucleic Acids Res. 50:1710078–92
    [Google Scholar]
  93. 93.
    Lee CH, Raghunathan K, Taylor GM, French AJ, Tenorio R et al. 2021. Reovirus nonstructural protein σNS recruits viral RNA to replication organelles. mBio 12:4e01408–21
    [Google Scholar]
  94. 94.
    Tauber D, Tauber G, Parker R. 2020. Mechanisms and regulation of RNA condensation in RNP granule formation. Trends Biochem. Sci. 45:9764–78
    [Google Scholar]
  95. 95.
    Marenduzzo D, Finan K, Cook PR. 2006. The depletion attraction: an underappreciated force driving cellular organization. J. Cell Biol. 175:5681–86
    [Google Scholar]
  96. 96.
    Van Treeck B, Parker R 2018. Emerging roles for intermolecular RNA-RNA interactions in RNP assemblies. Cell 174:4791–802
    [Google Scholar]
  97. 97.
    Goldberger O, Szoke T, Nussbaum-Shochat A, Amster-Choder O. 2022. Heterotypic phase separation of Hfq is linked to its roles as an RNA chaperone. Cell Rep. 41:13111881
    [Google Scholar]
  98. 98.
    Nott TJ, Petsalaki E, Farber P, Jervis D, Fussner E et al. 2015. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol. Cell 57:5936–47
    [Google Scholar]
  99. 99.
    Samir P, Kesavardhana S, Patmore DM, Gingras S, Malireddi RKS et al. 2019. DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome. Nature 573:7775590–94
    [Google Scholar]
  100. 100.
    Tauber D, Tauber G, Khong A, Van Treeck B, Pelletier J, Parker R. 2020. Modulation of RNA condensation by the DEAD-box protein eIF4A. Cell 180:3411–26.e16
    [Google Scholar]
  101. 101.
    Lin Y, Protter DSW, Rosen MK, Parker R. 2015. Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol. Cell 60:2208–19
    [Google Scholar]
  102. 102.
    Boeynaems S, Holehouse AS, Weinhardt V, Kovacs D, Van Lindt J et al. 2019. Spontaneous driving forces give rise to protein−RNA condensates with coexisting phases and complex material properties. PNAS 116:167889–98
    [Google Scholar]
  103. 103.
    McKell AO, LaConte LEW, McDonald SM. 2017. A temperature-sensitive lesion in the N-terminal domain of the rotavirus. J. Virol. 91:7e00062–17
    [Google Scholar]
  104. 104.
    Rao ALN. 2006. Genome packaging by spherical plant RNA viruses. Annu. Rev. Phytopathol. 44:61–87
    [Google Scholar]
  105. 105.
    Speir JA, Johnson JE. 2012. Nucleic acid packaging in viruses. Curr. Opin. Struct. Biol. 22:165–71
    [Google Scholar]
  106. 106.
    Bruinsma RF, Wuite GJL, Roos WH. 2021. Physics of viral dynamics. Nat. Rev. Phys. 3:276–91
    [Google Scholar]
  107. 107.
    Cadena-Nava RD, Comas-Garcia M, Garmann RF, Rao ALN, Knobler CM, Gelbart WM. 2012. Self-assembly of viral capsid protein and RNA molecules of different sizes: requirement for a specific high protein/RNA mass ratio. J. Virol. 86:63318–26
    [Google Scholar]
  108. 108.
    Garmann RF, Comas-Garcia M, Gopal A, Knobler CM, Gelbart WM. 2014. The assembly pathway of an icosahedral single-stranded RNA virus depends on the strength of inter-subunit attractions. J. Mol. Biol. 426:51050–60
    [Google Scholar]
  109. 109.
    McPherson A. 2005. Micelle formation and crystallization as paradigms for virus assembly. BioEssays 27:4447–58
    [Google Scholar]
  110. 110.
    Perlmutter JD, Hagan MF. 2015. Mechanisms of virus assembly. Annu. Rev. Phys. Chem. 66:217–39
    [Google Scholar]
  111. 111.
    Stroberg W, Schnell S. 2018. Do cellular condensates accelerate biochemical reactions? Lessons from microdroplet chemistry. Biophys. J. 115:13–8
    [Google Scholar]
  112. 112.
    Schmit JD, Michaels TCT. 2022. Physical limits to acceleration of chemical reactions inside phase-separated compartments. bioRxiv 2022.05.05.490822. https://doi.org/10.1101/2022.05.05.490822
  113. 113
    Cheung W, Gill M, Esposito A, Kaminski CF, Courousse N et al. 2010. Rotaviruses associate with cellular lipid droplet components to replicate in viroplasms, and compounds disrupting or blocking lipid droplets inhibit viroplasm formation and viral replication. J. Virol. 84:6782–98
    [Google Scholar]
  114. 114.
    Camus G, Vogt DA, Kondratowicz AS, Ott M. 2013. Lipid droplets and viral infections. Lipid Droplets H Yang, P Li 167–90. Amsterdam: Academic
    [Google Scholar]
  115. 115.
    Crawford SE, Desselberger U. 2016. Lipid droplets form complexes with viroplasms and are crucial for rotavirus replication. Curr. Opin. Virol. 19:11–15
    [Google Scholar]
  116. 116.
    Kniert J, dos Santos T, Eaton HE, Jung Cho W, Plummer G, Shmulevitz M 2022. Reovirus uses temporospatial compartmentalization to orchestrate core versus outercapsid assembly. PLOS Pathog. 18:9e1010641
    [Google Scholar]
  117. 117.
    Patton JT, Silvestri LS, Tortorici MA, Vasquez-Del Carpio R, Taraporewala ZF. 2006. Rotavirus genome replication and morphogenesis: role of the viroplasm. Reoviruses: Entry, Assembly and Morphogenesis P Roy 169–87. Berlin: Springer Berlin Heidelberg
    [Google Scholar]
  118. 118.
    Caspar DL. 1964. Assembly and stability of the tobacco mosaic virus particle. Adv. Protein Chem. 18:37–121
    [Google Scholar]
  119. 119.
    Chatterjee S, Maltseva D, Kan Y, Hosseini E, Gonella G et al. 2023. Lipid-driven condensation and interfacial ordering of FUS. Sci. Adv. 8:31eabm7528
    [Google Scholar]
  120. 120.
    Altenburg BC, Graham DY, Estes MK. 1980. Ultrastructural study of rotavirus replication in cultured cells. J. Gen. Virol. 46:75–85
    [Google Scholar]
  121. 121.
    Zhaoyang J, Hongyan S, Jianfei C, Da S, Jianbo L et al. 2021. Rotavirus viroplasm biogenesis involves microtubule-based dynein transport mediated by an interaction between NSP2 and dynein intermediate chain. J. Virol. 95:21e01246–21
    [Google Scholar]
  122. 122.
    Choudhury P, Bussiere LD, Miller CL. 2017. Mammalian orthoreovirus factories modulate stress granule protein localization by interaction with G3BP1. J. Virol. 91:21e01298–17
    [Google Scholar]
  123. 123.
    Poonam D, Durga RC. 2018. Rotavirus induces formation of remodeled stress granules and P bodies and their sequestration in viroplasms to promote progeny virus production. J. Virol. 92:24e01363–18
    [Google Scholar]
  124. 124.
    Maucuer A, Desforges B, Joshi V, Boca M, Kretov DA et al. 2018. Microtubules as platforms for probing liquid–liquid phase separation in cells—application to RNA-binding proteins. J. Cell Sci. 131:11jcs214692
    [Google Scholar]
  125. 125.
    King MR, Petry S. 2020. Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation. Nat. Commun. 11:1270
    [Google Scholar]
  126. 126.
    Walter H, Brooks DE. 1995. Phase separation in cytoplasm, due to macromolecular crowding, is the basis for microcompartmentation. FEBS Lett. 361:135–39
    [Google Scholar]
  127. 127.
    Chapman M, Liljas L 2003. Structural folds of viral proteins. Advances in Protein Chemistry: Virus Structure W Chiu, J Johnson 125–96. Amsterdam: Academic. , 1st ed..
    [Google Scholar]
  128. 128.
    Kondylis P, Schlicksup CJ, Brunk NE, Zhou J, Zlotnick A, Jacobson SC. 2019. Competition between normative and drug-induced virus self-assembly observed with single-particle methods. J. Am. Chem. Soc. 141:31251–60
    [Google Scholar]
  129. 129.
    Risso-Ballester J, Galloux M, Cao J, Le Goffic R, Hontonnou F et al. 2021. A condensate-hardening drug blocks RSV replication in vivo. Nature 595:7868596–99
    [Google Scholar]
  130. 130.
    Klein IA, Boija A, Afeyan LK, Hawken SW, Fan M et al. 2020. Partitioning of cancer therapeutics in nuclear condensates. Science 368:64971386–92
    [Google Scholar]
  131. 131.
    Wang S, Dai T, Qin Z, Pan T, Chu F et al. 2021. Targeting liquid–liquid phase separation of SARS-CoV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity. Nat. Cell Biol. 23:7718–32
    [Google Scholar]
  132. 132.
    Mitrea DM, Mittasch M, Gomes BF, Klein IA, Murcko MA. 2022. Modulating biomolecular condensates: a novel approach to drug discovery. Nat. Rev. Drug Discov. 21:11841–62
    [Google Scholar]
  133. 133.
    Gould SJ, Lewontin RC. 1979. The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc. R. Soc. B 205:581–98
    [Google Scholar]
  134. 134.
    Arter WE, Qi R, Erkamp NA, Krainer G, Didi K et al. 2022. Biomolecular condensate phase diagrams with a combinatorial microdroplet platform. Nat. Commun. 13:17845
    [Google Scholar]
  135. 135.
    Digman MA, Stakic M, Gratton E. 2013. Raster image correlation spectroscopy and number and brightness analysis. Methods Enzymol. 518:121–44
    [Google Scholar]
  136. 136.
    Ginell GM, Holehouse AS 2023. An introduction to the stickers-and-spacers framework as applied to biomolecular condensates. Phase-Separated Biomolecular Condensates: Methods and Protocols H-X Zhou, J-H Spille, PR Banerjee 95–116. New York: Springer
    [Google Scholar]
/content/journals/10.1146/annurev-virology-111821-103226
Loading
/content/journals/10.1146/annurev-virology-111821-103226
Loading

Data & Media loading...

Supplemental Material

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error