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Abstract

Viruses frequently carry out replication in specialized compartments within cells. The effect of these structures on virus replication is poorly understood. Recent research supports phase separation as a foundational principle for organization of cellular components with the potential to influence viral replication. In this review, phase separation is described in the context of formation of viral replication centers, with an emphasis on the nonsegmented negative-strand RNA viruses. Consideration is given to the interplay between phase separation and the critical processes of viral transcription and genome replication, and the role of these regions in pathogen-host interactions is discussed. Finally, critical questions that must be addressed to fully understand how phase separation influences viral replication and the viral life cycle are presented, along with information about new approaches that could be used to make important breakthroughs in this emerging field.

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2022-09-29
2024-12-11
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Literature Cited

  1. 1.
    Kopek BG, Settles EW, Friesen PD, Ahlquist P. 2010. Nodavirus-induced membrane rearrangement in replication complex assembly requires replicase protein A, RNA templates, and polymerase activity. J. Virol. 84:12492–503
    [Crossref] [Google Scholar]
  2. 2.
    McCartney AW, Greenwood JS, Fabian MR, White KA, Mullen RT. 2005. Localization of the tomato bushy stunt virus replication protein p33 reveals a peroxisome-to-endoplasmic reticulum sorting pathway. Plant Cell 17:3513–31
    [Crossref] [Google Scholar]
  3. 3.
    Miller S, Krijnse-Locker J. 2008. Modification of intracellular membrane structures for virus replication. Nat. Rev. Microbiol. 6:363–74
    [Crossref] [Google Scholar]
  4. 4.
    Paul D, Bartenschlager R. 2015. Flaviviridae replication organelles: oh, what a tangled web we weave. Annu. Rev. Virol. 2:289–310
    [Crossref] [Google Scholar]
  5. 5.
    Chukkapalli V, Randall G. 2014. Hepatitis C virus replication compartment formation: mechanism and drug target. Gastroenterology 146:1164–67
    [Crossref] [Google Scholar]
  6. 6.
    Hyde JL, Gillespie LK, Mackenzie JM. 2012. Mouse norovirus 1 utilizes the cytoskeleton network to establish localization of the replication complex proximal to the microtubule organizing center. J. Virol. 86:4110–22
    [Crossref] [Google Scholar]
  7. 7.
    Fontana J, López-Montero N, Elliott RM, Fernández JJ, Risco C. 2008. The unique architecture of Bunyamwera virus factories around the Golgi complex. Cell. Microbiol. 10:2012–28
    [Crossref] [Google Scholar]
  8. 8.
    Garmaroudi FS, Marchant D, Hendry R, Luo H, Yang D et al. 2015. Coxsackievirus B3 replication and pathogenesis. Future Microbiol 10:629–53
    [Crossref] [Google Scholar]
  9. 9.
    Sandoval IV, Carrasco L. 1997. Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the Golgi complex, the organelle target for the antipoliovirus drug Ro-090179. J. Virol. 71:4679–93
    [Crossref] [Google Scholar]
  10. 10.
    Roulin PS, Lötzerich M, Torta F, Tanner LB, van Kuppeveld FJ et al. 2014. Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface. Cell Host Microbe 16:677–90
    [Crossref] [Google Scholar]
  11. 11.
    Wolff G, Melia CE, Snijder EJ, Bárcena M. 2020. Double-membrane vesicles as platforms for viral replication. Trends Microbiol. 28:1022–33
    [Crossref] [Google Scholar]
  12. 12.
    Hidalgo P, Pimentel A, Mojica-Santamaría D, von Stromberg K, Hofmann-Sieber H et al. 2021. Evidence that the adenovirus single-stranded DNA binding protein mediates the assembly of biomolecular condensates to form viral replication compartments. Viruses 13:1778
    [Crossref] [Google Scholar]
  13. 13.
    Chang L, Godinez WJ, Kim I-H, Tektonidis M, de Lanerolle P et al. 2011. Herpesviral replication compartments move and coalesce at nuclear speckles to enhance export of viral late mRNA. PNAS 108:E136–44
    [Google Scholar]
  14. 14.
    Cziepluch C, Lampel S, Grewenig A, Grund C, Lichter P, Rommelaere J. 2000. H-1 parvovirus-associated replication bodies: a distinct virus-induced nuclear structure. J. Virol. 74:4807–15
    [Crossref] [Google Scholar]
  15. 15.
    Swindle CS, Zou N, Van Tine BA, Shaw GM, Engler JA, Chow LT. 1999. Human papillomavirus DNA replication compartments in a transient DNA replication system. J. Virol. 73:1001–9
    [Crossref] [Google Scholar]
  16. 16.
    Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M et al. 2012. Inclusion bodies are a site of ebolavirus replication. J. Virol. 86:11779–88
    [Crossref] [Google Scholar]
  17. 17.
    Dolnik O, Stevermann L, Kolesnikova L, Becker S. 2015. Marburg virus inclusions: a virus-induced microcompartment and interface to multivesicular bodies and the late endosomal compartment. Eur. J. Cell Biol. 94:323–31
    [Crossref] [Google Scholar]
  18. 18.
    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. 8:58
    [Crossref] [Google Scholar]
  19. 19.
    Wu X, Qi X, Liang M, Li C, Cardona CJ et al. 2014. Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus. FASEB J 28:2504–16
    [Crossref] [Google Scholar]
  20. 20.
    Zhou Y, Su JM, Samuel CE, Ma D. 2019. Measles virus forms inclusion bodies with properties of liquid organelles. J. Virol. 93:e00948–19
    [Google Scholar]
  21. 21.
    Ringel M, Heiner A, Behner L, Halwe S, Sauerhering L et al. 2019. Nipah virus induces two inclusion body populations: identification of novel inclusions at the plasma membrane. PLOS Pathog. 15:e1007733
    [Crossref] [Google Scholar]
  22. 22.
    Wadman M. 2018. The Vaccine Race: Science, Politics, and the Human Costs of Defeating Disease New York: Penguin
    [Google Scholar]
  23. 23.
    Pavelka M, Roth J. 2010. Viral inclusions. Functional Ultrastructure: Atlas of Tissue Biology and Pathology22–23 Vienna: Springer Vienna
    [Google Scholar]
  24. 24.
    Liu L. 2014. Fields Virology, , 6th edition.. Clin. Infect. Dis . 59613
    [Google Scholar]
  25. 25.
    Reissig M, Howes DW, Melnick JL. 1956. Sequence of morphological changes in epithelial cell cultures infected with poliovirus. J. Exp. Med. 104:289–304
    [Crossref] [Google Scholar]
  26. 26.
    Robbins FC, Enders JF, Weller TH. 1950. Cytopathogenic effect of poliomyelitis viruses in vitro on human embryonic tissues. Proc. Soc. Exp. Biol. Med. 75:370–74
    [Crossref] [Google Scholar]
  27. 27.
    Netherton C, Moffat K, Brooks E, Wileman T. 2007. A guide to viral inclusions, membrane rearrangements, factories, and viroplasm produced during virus replication. Adv. Virus Res. 70:101–82
    [Crossref] [Google Scholar]
  28. 28.
    Pinkerton H. 1950. The morphology of viral inclusions and their practical importance in the diagnosis of human disease. Am. J. Clin. Pathol. 20:201–7
    [Crossref] [Google Scholar]
  29. 29.
    Wileman T. 2007. Aggresomes and pericentriolar sites of virus assembly: cellular defense or viral design?. Annu. Rev. Microbiol. 61:149–67
    [Crossref] [Google Scholar]
  30. 30.
    Dolnik O, Gerresheim GK, Biedenkopf N. 2021. New perspectives on the biogenesis of viral inclusion bodies in negative-sense RNA virus infections. Cells 10:1460
    [Crossref] [Google Scholar]
  31. 31.
    Etibor TA, Yamauchi Y, Amorim MJ. 2021. Liquid biomolecular condensates and viral lifecycles: review and perspectives. Viruses 13:366
    [Crossref] [Google Scholar]
  32. 32.
    Lopez N, Camporeale G, Salgueiro M, Borkosky SS, Visentin A et al. 2021. Deconstructing virus condensation. PLOS Pathog 17:e1009926
    [Crossref] [Google Scholar]
  33. 33.
    Nevers Q, Albertini AA, Lagaudriere-Gesbert C, Gaudin Y. 2020. Negri bodies and other virus membrane-less replication compartments. Biochim. Biophys. Acta Mol. Cell Res. 1867:118831
    [Crossref] [Google Scholar]
  34. 34.
    Su JM, Wilson MZ, Samuel CE, Ma D. 2021. Formation and function of liquid-like viral factories in negative-sense single-stranded RNA virus infections. Viruses 13:126
    [Crossref] [Google Scholar]
  35. 35.
    Choi J-M, Holehouse AS, Pappu RV. 2020. Physical principles underlying the complex biology of intracellular phase transitions. Annu. Rev. Biophys. 49:107–33
    [Crossref] [Google Scholar]
  36. 36.
    Bergeron-Sandoval L-P, Kumar S, Heris HK, Chang CLA, Cornell CE et al. 2021. Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling. PNAS 118:e2113789118
    [Crossref] [Google Scholar]
  37. 37.
    Sanders DW, Kedersha N, Lee DSW, Strom AR, Drake V et al. 2020. Competing protein-RNA interaction networks control multiphase intracellular organization. Cell 181:306–24.e28
    [Crossref] [Google Scholar]
  38. 38.
    Jawerth L, Fischer-Friedrich E, Saha S, Wang J, Franzmann T et al. 2020. Protein condensates as aging Maxwell fluids. Science 370:1317–23
    [Crossref] [Google Scholar]
  39. 38a.
    Mittag T, Pappu RV 2022. A conceptual framework for understanding phase separation and addressing open questions and challenges. Mol. Cell 82:12220114
    [Crossref] [Google Scholar]
  40. 39.
    Hyman AA, Weber CA, Jülicher F. 2014. Liquid-liquid phase separation in biology. Annu. Rev. Cell Dev. Biol. 30:39–58
    [Crossref] [Google Scholar]
  41. 40.
    Dignon GL, Best RB, Mittal J. 2020. Biomolecular phase separation: from molecular driving forces to macroscopic properties. Annu. Rev. Phys. Chem. 71:53–75
    [Crossref] [Google Scholar]
  42. 41.
    Lyon AS, Peeples WB, Rosen MK. 2021. A framework for understanding the functions of biomolecular condensates across scales. Nat. Rev. Mol. Cell Biol. 22:215–35
    [Crossref] [Google Scholar]
  43. 42.
    Chong PA, Forman-Kay JD. 2016. Liquid-liquid phase separation in cellular signaling systems. Curr. Opin. Struct. Biol. 41:180–86
    [Crossref] [Google Scholar]
  44. 43.
    Alberti S. 2017. Phase separation in biology. Curr. Biol. 27:R1097–102
    [Crossref] [Google Scholar]
  45. 44.
    Alberti S, Dormann D. 2019. Liquid-liquid phase separation in disease. Annu. Rev. Genet. 53:171–94
    [Crossref] [Google Scholar]
  46. 45.
    Andre AAM, Spruijt E. 2020. Liquid-liquid phase separation in crowded environments. Int. J. Mol. Sci. 21:5908
    [Crossref] [Google Scholar]
  47. 46.
    Banani SF, Lee HO, Hyman AA, Rosen MK. 2017. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18:285–98
    [Crossref] [Google Scholar]
  48. 47.
    Li P, Banjade S, Cheng HC, Kim S, Chen B et al. 2012. Phase transitions in the assembly of multivalent signalling proteins. Nature 483:336–40
    [Crossref] [Google Scholar]
  49. 48.
    Klosin A, Oltsch F, Harmon T, Honigmann A, Jülicher F et al. 2020. Phase separation provides a mechanism to reduce noise in cells. Science 367:6476464–68
    [Crossref] [Google Scholar]
  50. 49.
    Martin EW, Holehouse AS, Peran I, Farag M, Incicco JJ et al. 2020. Valence and patterning of aromatic residues determine the phase behavior of prion-like domains. Science 367:694–99
    [Crossref] [Google Scholar]
  51. 50.
    Martin EW, Holehouse AS. 2020. Intrinsically disordered protein regions and phase separation: sequence determinants of assembly or lack thereof. Emerg. Top. Life Sci. 4:307–29
    [Crossref] [Google Scholar]
  52. 51.
    Lin Y, Protter DS, Rosen MK, Parker R. 2015. Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol. Cell 60:208–19
    [Crossref] [Google Scholar]
  53. 52.
    Na Z, Luo Y, Cui DS, Khitun A, Smelyansky S et al. 2021. Phosphorylation of a human microprotein promotes dissociation of biomolecular condensates. J. Am. Chem. Soc. 143:12675–87
    [Crossref] [Google Scholar]
  54. 53.
    Dao TP, Kolaitis RM, Kim HJ, O'Donovan K, Martyniak B et al. 2018. Ubiquitin modulates liquid-liquid phase separation of UBQLN2 via disruption of multivalent interactions. Mol. Cell 69:965–78.e6
    [Crossref] [Google Scholar]
  55. 54.
    Han D, Longhini AP, Zhang X, Hoang V, Wilson MZ, Kosik KS. 2022. Dynamic assembly of the mRNA m6A methyltransferase complex is regulated by METTL3 phase separation. PLOS Biol. 20:e3001535
    [Crossref] [Google Scholar]
  56. 55.
    Patel A, Lee HO, Jawerth L, Maharana S, Jahnel M et al. 2015. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162:1066–77
    [Crossref] [Google Scholar]
  57. 56.
    Wheeler JR, Matheny T, Jain S, Abrisch R, Parker R. 2016. Distinct stages in stress granule assembly and disassembly. eLife 5:e18413
    [Crossref] [Google Scholar]
  58. 57.
    Luo Y, Na Z, Slavoff SA 2018. P-bodies: composition, properties, and functions. Biochemistry 57:2424–31
    [Crossref] [Google Scholar]
  59. 58.
    Yu H, Lu S, Gasior K, Singh D, Vazquez-Sanchez S et al. 2021. HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science 371:eabb4309
    [Crossref] [Google Scholar]
  60. 59.
    Patel A, Malinovska L, Saha S, Wang J, Alberti S et al. 2017. ATP as a biological hydrotrope. Science 356:753–56
    [Crossref] [Google Scholar]
  61. 60.
    Boczek EE, Fürsch J, Niedermeier ML, Jawerth L, Jahnel M et al. 2021. HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA-binding domain. eLife 10:e69377
    [Crossref] [Google Scholar]
  62. 61.
    Lahaye X, Vidy A, Pomier C, Obiang L, Harper F et al. 2009. Functional characterization of Negri bodies (NBs) in rabies virus-infected cells: evidence that NBs are sites of viral transcription and replication. J. Virol. 83:7948–58
    [Crossref] [Google Scholar]
  63. 62.
    Nikolic J, Le Bars R, Lama Z, Scrima N, Lagaudriere-Gesbert C et al. 2017. Negri bodies are viral factories with properties of liquid organelles. Nat. Commun. 8:58
    [Crossref] [Google Scholar]
  64. 63.
    Heinrich BS, Cureton DK, Rahmeh AA, Whelan SP. 2010. Protein expression redirects vesicular stomatitis virus RNA synthesis to cytoplasmic inclusions. PLOS Pathog 6:e1000958
    [Crossref] [Google Scholar]
  65. 64.
    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
    [Crossref] [Google Scholar]
  66. 65.
    Kurtzke JF. 1956. Inclusion body encephalitis: a nonfatal case. Neurology 6:371
    [Crossref] [Google Scholar]
  67. 66.
    Guseva S, Milles S, Jensen MR, Schoehn G, Ruigrok RW, Blackledge M. 2020. Structure, dynamics and phase separation of measles virus RNA replication machinery. Curr. Opin. Virol. 41:59–67
    [Crossref] [Google Scholar]
  68. 67.
    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:eaaz7095
    [Crossref] [Google Scholar]
  69. 68.
    Carlos TS, Young DF, Schneider M, Simas JP, Randall RE. 2009. Parainfluenza virus 5 genomes are located in viral cytoplasmic bodies whilst the virus dismantles the interferon-induced antiviral state of cells. J. Gen. Virol. 90:2147–56
    [Crossref] [Google Scholar]
  70. 69.
    Li Y, Zhang C, Lu N, Deng X, Zang G et al. 2019. Involvement of actin-regulating factor cofilin in the inclusion body formation and RNA synthesis of human parainfluenza virus type 3 via interaction with the nucleoprotein. Front. Microbiol. 10:95
    [Crossref] [Google Scholar]
  71. 70.
    Zhang S, Jiang Y, Cheng Q, Zhong Y, Qin Y, Chen M. 2017. Inclusion body fusion of human parainfluenza virus type 3 regulated by acetylated α-tubulin enhances viral replication. J. Virol. 91:e01802–16
    [Google Scholar]
  72. 71.
    Galloux M, Risso-Ballester J, Richard CA, Fix J, Rameix-Welti MA, Eleouet JF. 2020. Minimal elements required for the formation of respiratory syncytial virus cytoplasmic inclusion bodies in vivo and in vitro. mBio 11:e01202–20
    [Crossref] [Google Scholar]
  73. 72.
    Rincheval V, Lelek M, Gault E, Bouillier C, Sitterlin D et al. 2017. Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus. Nat. Commun. 8:563
    [Crossref] [Google Scholar]
  74. 73.
    Derdowski A, Peters TR, Glover N, Qian R, Utley TJ et al. 2008. Human metapneumovirus nucleoprotein and phosphoprotein interact and provide the minimal requirements for inclusion body formation. J. Gen. Virol. 89:2698–708
    [Crossref] [Google Scholar]
  75. 74.
    Cifuentes-Munoz N, Branttie J, Slaughter KB, Dutch RE. 2017. Human metapneumovirus induces formation of inclusion bodies for efficient genome replication and transcription. J. Virol. 91:e01282–17
    [Google Scholar]
  76. 75.
    Boggs KB, Cifuentes-Munoz N, Edmonds K, El Najjar F, Ossandon C et al. 2021. Human metapneumovirus P protein independently drives phase separation and recruits N protein to liquid-like inclusion bodies. bioRxiv 2021.09.24.461765. https://doi.org/10.1101/2021.09.24.461765
    [Crossref]
  77. 76.
    Miyake T, Farley CM, Neubauer BE, Beddow TP, Hoenen T et al. 2020. Ebola virus inclusion body formation and RNA synthesis are controlled by a novel domain of nucleoprotein interacting with VP35. J. Virol. 94:e02100–19
    [Crossref] [Google Scholar]
  78. 77.
    Schmidt ML, Hoenen T. 2017. Characterization of the catalytic center of the Ebola virus L polymerase. PLOS Negl. Trop. Dis. 11:e0005996
    [Crossref] [Google Scholar]
  79. 78.
    Papa G, Borodavka A, Desselberger U. 2021. Viroplasms: assembly and functions of rotavirus replication factories. Viruses 13:1349
    [Crossref] [Google Scholar]
  80. 79.
    Geiger F, Acker J, Papa G, Wang X, Arter WEet al 2021. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. EMBO J 40:e107711
    [Crossref] [Google Scholar]
  81. 80.
    Eichwald C, Arnoldi F, Laimbacher AS, Schraner EM, Fraefel C et al. 2012. Rotavirus viroplasm fusion and perinuclear localization are dynamic processes requiring stabilized microtubules. PLOS ONE 7:e47947
    [Crossref] [Google Scholar]
  82. 81.
    Criglar JM, Crawford SE, Zhao B, Smith HG, Stossi F et al. 2020. A genetically engineered rotavirus NSP2 phosphorylation mutant impaired in viroplasm formation and replication shows an early interaction between vNSP2 and cellular lipid droplets. J. Virol. 94:e00972–20
    [Crossref] [Google Scholar]
  83. 82.
    Carlson CR, Asfaha JB, Ghent CM, Howard CJ, Hartooni N et al. 2020. Phosphoregulation of phase separation by the SARS-CoV-2 N protein suggests a biophysical basis for its dual functions. Mol. Cell 80:1092–103.e4
    [Crossref] [Google Scholar]
  84. 83.
    Cubuk J, Alston JJ, Incicco JJ, Singh S, Stuchell-Brereton MD et al. 2021. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nat. Commun. 12:1936
    [Crossref] [Google Scholar]
  85. 84.
    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 80:1078–91.e6
    [Crossref] [Google Scholar]
  86. 85.
    Jack A, Ferro LS, Trnka MJ, Wehri E, Nadgir A et al. 2021. SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA. PLOS Biol 19:e3001425
    [Crossref] [Google Scholar]
  87. 86.
    Lu S, Ye Q, Singh D, Cao Y, Diedrich JK et al. 2021. The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nat. Commun. 12:502
    [Crossref] [Google Scholar]
  88. 87.
    Perdikari TM, Murthy AC, Ryan VH, Watters S, Naik MT, Fawzi NL. 2020. SARS-CoV-2 nucleocapsid protein phase-separates with RNA and with human hnRNPs. EMBO J 39:e106478
    [Crossref] [Google Scholar]
  89. 88.
    Wu C, Qavi AJ, Hachim A, Kavian N, Cole AR et al. 2021. Characterization of SARS-CoV-2 nucleocapsid protein reveals multiple functional consequences of the C-terminal domain. iScience 24:102681
    [Crossref] [Google Scholar]
  90. 89.
    Monette A, Niu M, Chen L, Rao S, Gorelick RJ, Mouland AJ. 2020. Pan-retroviral nucleocapsid-mediated phase separation regulates genomic RNA positioning and trafficking. Cell Rep 31:107520
    [Crossref] [Google Scholar]
  91. 90.
    Metrick CM, Koenigsberg AL, Heldwein EE. 2020. Conserved outer tegument component UL11 from herpes simplex virus 1 is an intrinsically disordered, RNA-binding protein. mBio 11:e00810–20
    [Crossref] [Google Scholar]
  92. 91.
    Castagné N, Barbier A, Bernard J, Rezaei H, Huet JC et al. 2004. Biochemical characterization of the respiratory syncytial virus P-P and P-N protein complexes and localization of the P protein oligomerization domain. J. Gen. Virol. 85:1643–53
    [Crossref] [Google Scholar]
  93. 92.
    Su Z, Wu C, Shi L, Luthra P, Pintilie GD et al. 2018. Electron cryo-microscopy structure of Ebola virus nucleoprotein reveals a mechanism for nucleocapsid-like assembly. Cell 172:966–78.e12
    [Crossref] [Google Scholar]
  94. 93.
    Leung DW, Borek D, Luthra P, Binning JM, Anantpadma M et al. 2015. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions. Cell Rep. 11:376–89
    [Crossref] [Google Scholar]
  95. 94.
    Bankamp B, Horikami SM, Thompson PD, Huber M, Billeter M, Moyer SA. 1996. Domains of the measles virus N protein required for binding to P protein and self-assembly. Virology 216:272–77
    [Crossref] [Google Scholar]
  96. 95.
    Tawar RG, Duquerroy S, Vonrhein C, Varela PF, Damier-Piolle L et al. 2009. Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science 326:1279–83
    [Crossref] [Google Scholar]
  97. 96.
    Pyle JD, Whelan SPJ, Bloyet LM. 2021. Structure and function of negative-strand RNA virus polymerase complexes. Enzymes 50:21–78
    [Crossref] [Google Scholar]
  98. 97.
    Luthra P, Jordan DS, Leung DW, Amarasinghe GK, Basler CF. 2015. Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis. J. Virol. 89:5148–53
    [Crossref] [Google Scholar]
  99. 98.
    Chanthamontri CK, Jordan DS, Wang W, Wu C, Lin Y et al. 2019. The Ebola viral protein 35 N-terminus is a parallel tetramer. Biochemistry 58:657–64
    [Crossref] [Google Scholar]
  100. 99.
    Bloyet LM, Schramm A, Lazert C, Raynal B, Hologne M et al. 2019. Regulation of measles virus gene expression by P protein coiled-coil properties. Sci. Adv. 5:eaaw3702
    [Crossref] [Google Scholar]
  101. 100.
    Nilsson-Payant BE, Blanco-Melo D, Uhl S, Escudero-Pérez B, Olschewski S et al. 2021. Reduced nucleoprotein availability impairs negative-sense RNA virus replication and promotes host recognition. J. Virol. 95:e02274–20
    [Google Scholar]
  102. 101.
    Fearns R, Peeples ME, Collins PL. 1997. Increased expression of the N protein of respiratory syncytial virus stimulates minigenome replication but does not alter the balance between the synthesis of mRNA and antigenome. Virology 236:188–201
    [Crossref] [Google Scholar]
  103. 102.
    Cressey TN, Noton SL, Nagendra K, Braun MR, Fearns R. 2018. Mechanism for de novo initiation at two sites in the respiratory syncytial virus promoter. Nucleic Acids Res 46:6785–96
    [Crossref] [Google Scholar]
  104. 103.
    Lifland AW, Jung J, Alonas E, Zurla C, Crowe JE Jr., Santangelo PJ. 2012. Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS. J. Virol. 86:8245–58
    [Crossref] [Google Scholar]
  105. 104.
    Sankaranarayanan M, Emenecker RJ, Wilby EL, Jahnel M, Trussina I et al. 2021. Adaptable P body physical states differentially regulate bicoid mRNA storage during early Drosophila development. Dev. Cell 56:2886–901.e6
    [Crossref] [Google Scholar]
  106. 105.
    Nikolic J, Civas A, Lama Z, Lagaudriere-Gesbert C, Blondel D. 2016. Rabies virus infection induces the formation of stress granules closely connected to the viral factories. PLOS Pathog 12:e1005942
    [Crossref] [Google Scholar]
  107. 106.
    Bloyet LM, Welsch J, Enchery F, Mathieu C, de Breyne S et al. 2016. HSP90 chaperoning in addition to phosphoprotein required for folding but not for supporting enzymatic activities of measles and Nipah virus L polymerases. J. Virol. 90:6642–56
    [Crossref] [Google Scholar]
  108. 107.
    Munday DC, Wu W, Smith N, Fix J, Noton SL et al. 2015. Interactome analysis of the human respiratory syncytial virus RNA polymerase complex identifies protein chaperones as important cofactors that promote L-protein stability and RNA synthesis. J. Virol. 89:917–30
    [Crossref] [Google Scholar]
  109. 108.
    Katoh H, Kubota T, Nakatsu Y, Tahara M, Kidokoro M, Takeda M. 2017. Heat shock protein 90 ensures efficient mumps virus replication by assisting with viral polymerase complex formation. J. Virol. 91:e02220–16
    [Crossref] [Google Scholar]
  110. 109.
    Jobe F, Simpson J, Hawes P, Guzman E, Bailey D. 2020. Respiratory syncytial virus sequesters NF-κB subunit p65 to cytoplasmic inclusion bodies to inhibit innate immune signaling. J. Virol. 94:e01380–20
    [Crossref] [Google Scholar]
  111. 110.
    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. 10:1629
    [Crossref] [Google Scholar]
  112. 111.
    Cifuentes-Munoz N, Dutch RE, Cattaneo R. 2018. Direct cell-to-cell transmission of respiratory viruses: the fast lanes. PLOS Pathog 14:e1007015
    [Crossref] [Google Scholar]
  113. 112.
    El Najjar F, Cifuentes-Muñoz N, Chen J, Zhu H, Buchholz UJ et al. 2016. Human metapneumovirus induces reorganization of the actin cytoskeleton for direct cell-to-cell spread. PLOS Pathog 12:e1005922
    [Crossref] [Google Scholar]
  114. 113.
    Novoa RR, Calderita G, Cabezas P, Elliott RM, Risco C. 2005. Key Golgi factors for structural and functional maturation of bunyamwera virus. J. Virol. 79:10852–63
    [Crossref] [Google Scholar]
  115. 114.
    Barbosa NS, Mendonça LR, Dias MVS, Pontelli MC, da Silva EZM et al. 2018. ESCRT machinery components are required for Orthobunyavirus particle production in Golgi compartments. PLOS Pathog 14:e1007047
    [Crossref] [Google Scholar]
  116. 115.
    Li Z, Guo D, Qin Y, Chen M. 2019. PI4KB on inclusion bodies formed by ER membrane remodeling facilitates replication of human parainfluenza virus type 3. Cell Rep. 29:2229–42.e4
    [Crossref] [Google Scholar]
  117. 116.
    Kawai T, Akira S. 2006. Innate immune recognition of viral infection. Nat. Immunol. 7:131–37
    [Crossref] [Google Scholar]
  118. 117.
    Chatterjee S, Basler CF, Amarasinghe GK, Leung DW. 2016. Molecular mechanisms of innate immune inhibition by non-segmented negative-sense RNA viruses. J. Mol. Biol. 428:3467–82
    [Crossref] [Google Scholar]
  119. 118.
    Ménager P, Roux P, Mégret F, Bourgeois JP, Le Sourd AM et al. 2009. Toll-like receptor 3 (TLR3) plays a major role in the formation of rabies virus Negri Bodies. PLOS Pathog 5:e1000315
    [Crossref] [Google Scholar]
  120. 119.
    Fearns R, Young DF, Randall RE. 1994. Evidence that the paramyxovirus simian virus 5 can establish quiescent infections by remaining inactive in cytoplasmic inclusion bodies. J. Gen. Virol. 75:Part 123525–39
    [Crossref] [Google Scholar]
  121. 120.
    Nilsson-Payant BE, Blanco-Melo D, Uhl S, Escudero-Perez B, Olschewski S et al. 2021. Reduced nucleoprotein availability impairs negative-sense RNA virus replication and promotes host recognition. J. Virol. 95:e02274–20
    [Google Scholar]
  122. 121.
    Xue M, Zhao BS, Zhang Z, Lu M, Harder O et al. 2019. Viral N6-methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus. Nat. Commun. 10:4595
    [Crossref] [Google Scholar]
  123. 122.
    Xue M, Zhang Y, Wang H, Kairis EL, Lu M et al. 2021. Viral RNA N6-methyladenosine modification modulates both innate and adaptive immune responses of human respiratory syncytial virus. PLoS Pathog. 17:12e1010142
    [Crossref] [Google Scholar]
  124. 123.
    Lu M, Zhang Z, Xue M, Zhao BS, Harder O et al. 2020. N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I. Nat. Microbiol. 5:584–98
    [Crossref] [Google Scholar]
  125. 124.
    Lu M, Xue M, Wang HT, Kairis EL, Ahmad S et al. 2021. Nonsegmented negative-sense RNA viruses utilize N6-methyladenosine (m6A) as a common strategy to evade host innate immunity. J. Virol. 95:e02274–20
    [Google Scholar]
  126. 125.
    Brzozka K, Finke S, Conzelmann KK. 2006. Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. J. Virol. 80:2675–83
    [Crossref] [Google Scholar]
  127. 126.
    Vidy A, Chelbi-Alix M, Blondel D. 2005. Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways. J. Virol. 79:14411–20
    [Crossref] [Google Scholar]
  128. 127.
    Brzozka K, Finke S, Conzelmann KK. 2005. Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3. J. Virol. 79:7673–81
    [Crossref] [Google Scholar]
  129. 128.
    Hong Y, Bai M, Qi X, Li C, Liang M et al. 2019. Suppression of the IFN-α and -β induction through sequestering IRF7 into viral inclusion bodies by nonstructural protein NSs in severe fever with thrombocytopenia syndrome bunyavirus infection. J. Immunol. 202:841–56
    [Crossref] [Google Scholar]
  130. 129.
    Feng Z, Cerveny M, Yan Z, He B 2007. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J. Virol. 81:182–92
    [Crossref] [Google Scholar]
  131. 130.
    Hume A, Muhlberger E. 2018. Marburg virus viral protein 35 inhibits protein kinase R activation in a cell type–specific manner. J. Infect. Dis. 218:S403–8
    [Google Scholar]
  132. 131.
    Fricke J, Koo LY, Brown CR, Collins PL. 2013. p38 and OGT sequestration into viral inclusion bodies in cells infected with human respiratory syncytial virus suppresses MK2 activities and stress granule assembly. J. Virol. 87:1333–47
    [Crossref] [Google Scholar]
  133. 132.
    Nelson EV, Schmidt KM, Deflube LR, Doganay S, Banadyga L et al. 2016. Ebola virus does not induce stress granule formation during infection and sequesters stress granule proteins within viral inclusions. J. Virol. 90:7268–84
    [Crossref] [Google Scholar]
  134. 133.
    Ning YJ, Wang M, Deng M, Shen S, Liu W et al. 2014. Viral suppression of innate immunity via spatial isolation of TBK1/IKKε from mitochondrial antiviral platform. J. Mol. Cell Biol. 6:324–37
    [Crossref] [Google Scholar]
  135. 134.
    Khairil Anuar INA, Banerjee A, Keeble AH, Carella A, Nikov GI, Howarth M. 2019. Spy&Go purification of SpyTag-proteins using pseudo-SpyCatcher to access an oligomerization toolbox. Nat. Commun. 10:1734
    [Crossref] [Google Scholar]
  136. 135.
    Bracha D, Walls MT, Wei M-T, Zhu L, Kurian M et al. 2018. Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds. Cell 175:1467–80.e13
    [Crossref] [Google Scholar]
  137. 136.
    Garabedian MV, Wang W, Dabdoub JB, Tong M, Caldwell RM et al. 2021. Designer membraneless organelles sequester native factors for control of cell behavior. Nat. Chem. Biol. 17:998–1007
    [Crossref] [Google Scholar]
  138. 137.
    Hastings RL, Boeynaems S. 2021. Designer condensates: a toolkit for the biomolecular architect. J. Mol. Biol. 433:12166837
    [Crossref] [Google Scholar]
  139. 138.
    Subach FV, Subach OM, Gundorov IS, Morozova KS, Piatkevich KD et al. 2009. Monomeric fluorescent timers that change color from blue to red report on cellular trafficking. Nat. Chem. Biol. 5:118–26
    [Crossref] [Google Scholar]
  140. 139.
    Youn JY, Dyakov BJA, Zhang J, Knight JDR, Vernon RM et al. 2019. Properties of stress granule and P-body proteomes. Mol. Cell 76:286–94
    [Crossref] [Google Scholar]
  141. 140.
    Hung V, Udeshi ND, Lam SS, Loh KH, Cox KJ et al. 2016. Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nat. Protoc. 11:456–75
    [Crossref] [Google Scholar]
  142. 141.
    Martell JD, Deerinck TJ, Lam SS, Ellisman MH, Ting AY. 2017. Electron microscopy using the genetically encoded APEX2 tag in cultured mammalian cells. Nat. Protoc. 12:1792–816
    [Crossref] [Google Scholar]
  143. 142.
    de Boer P, Hoogenboom JP, Giepmans BNG. 2015. Correlated light and electron microscopy: ultrastructure lights up!. Nat. Methods 12:503–13
    [Crossref] [Google Scholar]
  144. 143.
    Wan W, Briggs JAG. 2016. Cryo-electron tomography and subtomogram averaging. Methods Enzymol. 579:329–67
    [Crossref] [Google Scholar]
  145. 144.
    Randall RE, Griffin DE. 2017. Within host RNA virus persistence: mechanisms and consequences. Curr. Opin. Virol. 23:35–42
    [Crossref] [Google Scholar]
  146. 145.
    Young DF, Wignall-Fleming EB, Busse DC, Pickin MJ, Hankinson J et al. 2019. The switch between acute and persistent paramyxovirus infection caused by single amino acid substitutions in the RNA polymerase P subunit. PLOS Pathog 15:e1007561
    [Crossref] [Google Scholar]
  147. 146.
    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 595:596–99
    [Crossref] [Google Scholar]
  148. 147.
    Carey JL, Guo L. 2022. Liquid-liquid phase separation of TDP-43 and FUS in physiology and pathology of neurodegenerative diseases. Front. Mol. Biosci. 9:826719
    [Crossref] [Google Scholar]
  149. 148.
    Boyko S, Surewicz WK. 2022. Tau liquid–liquid phase separation in neurodegenerative diseases. Trends Cell Biol 2022: https://doi.org/10.1016/j.tcb.2022.01.011
    [Crossref] [Google Scholar]
  150. 149.
    Tenorio R, Fernández de Castro I, Knowlton JJ, Zamora PF, Lee CH et al. 2018. Proteins remodel the endoplasmic reticulum to build replication neo-organelles. . mBio 9:4e01253–18
    [Crossref] [Google Scholar]
  151. 150.
    Papa G, Borodavka A, Desselberger U. 2021. Viroplasms: assembly and functions of rotavirus replication factories. Viruses. 13:71349
    [Crossref] [Google Scholar]
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