Skip to main content
SpringerLink
Log in

Structure and Function of Negri Bodies

  • Chapter
  • First Online:
Physical Virology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1215))

Abstract

Replication and assembly of many viruses occur in viral factories which are specialized intracellular compartments formed during viral infection. For rabies virus, those viral factories are called Negri bodies (NBs). NBs are cytoplasmic inclusion bodies in which viral RNAs (mRNAs as well as genomic and antigenomic RNAs) are synthesized. NBs are spherical, they can fuse together, and can reversibly deform when encountering a physical barrier. All these characteristics are similar to those of eukaryotic membrane-less liquid organelles which contribute to the compartmentalization of the cell interior. Indeed, the liquid nature of NBs has been confirmed by FRAP experiments. The co-expression of rabies virus nucleoprotein N and phosphoprotein P is sufficient to induce the formation of cytoplasmic inclusions recapitulating NBs properties. Remarkably, P and N have features similar to those of cellular proteins involved in liquid organelles formation: N is an RNA-binding protein and P contains intrinsically disordered domains. An overview of the literature indicates that formation of liquid viral factories by phase separation is probably common among Mononegavirales. This allows specific recruitment and concentration of viral proteins. Finally, as virus-associated molecular patterns recognized by cellular sensors of RNA virus replication are probably essentially present in the viral factory, there should be a subtle interplay (which remains to be characterized) between those liquid structures and the cellular proteins which trigger the innate immune response.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

aa:

Amino acid

BHK21:

Baby Hamster Kidney 21 cells

FAK:

Focal adhesion kinase

FRAP:

Fluorescence recovery after photobleaching

IDD:

Intrinsically disordered domain

le:

Leader RNA

NB:

Negri body

PML:

Promyelocytic leukemia protein

RABV:

Rabies virus

RdRP:

RNA-dependent RNA polymerase

RNP:

Ribonucleoprotein

VSV:

Vesicular stomatitis virus

References

  1. Netherton CL, Wileman T (2011) Virus factories, double membrane vesicles and viroplasm generated in animal cells. Curr Opin Virol 1(5):381–387. https://doi.org/10.1016/j.coviro.2011.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Novoa RR, Calderita G, Arranz R, Fontana J, Granzow H, Risco C (2005) Virus factories: associations of cell organelles for viral replication and morphogenesis. Biol Cell 97(2):147–172. https://doi.org/10.1042/BC20040058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chinchar VG, Hyatt A, Miyazaki T, Williams T (2009) Family Iridoviridae: poor viral relations no longer. Curr Top Microbiol Immunol 328:123–170

    CAS  PubMed  Google Scholar 

  4. Risco C, Rodriguez JR, Lopez-Iglesias C, Carrascosa JL, Esteban M, Rodriguez D (2002) Endoplasmic reticulum-Golgi intermediate compartment membranes and vimentin filaments participate in vaccinia virus assembly. J Virol 76(4):1839–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rojo G, Garcia-Beato R, Vinuela E, Salas ML, Salas J (1999) Replication of African swine fever virus DNA in infected cells. Virology 257(2):524–536

    Article  CAS  PubMed  Google Scholar 

  6. Schramm B, Locker JK (2005) Cytoplasmic organization of POXvirus DNA replication. Traffic 6(10):839–846. https://doi.org/10.1111/j.1600-0854.2005.00324.x

    Article  CAS  PubMed  Google Scholar 

  7. Wileman T (2007) Aggresomes and pericentriolar sites of virus assembly: cellular defense or viral design? Annu Rev Microbiol 61:149–167. https://doi.org/10.1146/annurev.micro.57.030502.090836

    Article  CAS  PubMed  Google Scholar 

  8. Avila-Perez G, Rejas MT, Rodriguez D (2016) Ultrastructural characterization of membranous torovirus replication factories. Cell Microbiol 18(12):1691–1708. https://doi.org/10.1111/cmi.12620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Harak C, Lohmann V (2015) Ultrastructure of the replication sites of positive-strand RNA viruses. Virology 479-480:418–433. https://doi.org/10.1016/j.virol.2015.02.029

    Article  CAS  PubMed  Google Scholar 

  10. Kopek BG, Perkins G, Miller DJ, Ellisman MH, Ahlquist P (2007) Three-dimensional analysis of a viral RNA replication complex reveals a virus-induced mini-organelle. PLoS Biol 5(9):e220. https://doi.org/10.1371/journal.pbio.0050220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Heinrich BS, Cureton DK, Rahmeh AA, Whelan SP (2010) Protein expression redirects vesicular stomatitis virus RNA synthesis to cytoplasmic inclusions. PLoS Pathog 6(6):e1000958. https://doi.org/10.1371/journal.ppat.1000958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lahaye X, Vidy A, Pomier C, Obiang L, Harper F, Gaudin Y, Blondel D (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(16):7948–7958. https://doi.org/10.1128/JVI.00554-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Menager P, Roux P, Megret F, Bourgeois JP, Le Sourd AM, Danckaert A, Lafage M, Prehaud C, Lafon M (2009) Toll-like receptor 3 (TLR3) plays a major role in the formation of rabies virus Negri Bodies. PLoS Pathog 5(2):e1000315. https://doi.org/10.1371/journal.ppat.1000315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M, Schudt G, Dolnik O, Basler CF, Becker S, Feldmann H (2012) Inclusion bodies are a site of ebolavirus replication. J Virol 86(21):11779–11788. https://doi.org/10.1128/JVI.01525-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rincheval V, Lelek M, Gault E, Bouillier C, Sitterlin D, Blouquit-Laye S, Galloux M, Zimmer C, Eleouet JF, Rameix-Welti MA (2017) Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus. Nat Commun 8(1):563. https://doi.org/10.1038/s41467-017-00655-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Negri A (1903) Contributo allo studio dell’ eziologia della rabia. Bol Soc Med Chir Pavia 2:88–114

    Google Scholar 

  17. Dietzgen RG, Kondo H, Goodin MM, Kurath G, Vasilakis N (2017) The family Rhabdoviridae: mono- and bipartite negative-sense RNA viruses with diverse genome organization and common evolutionary origins. Virus Res 227:158–170. https://doi.org/10.1016/j.virusres.2016.10.010

    Article  CAS  PubMed  Google Scholar 

  18. Cureton DK, Massol RH, Saffarian S, Kirchhausen TL, Whelan SP (2009) Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog 5(4):e1000394

    Article  PubMed  PubMed Central  Google Scholar 

  19. Johannsdottir HK, Mancini R, Kartenbeck J, Amato L, Helenius A (2009) Host cell factors and functions involved in vesicular stomatitis virus entry. J Virol 83(1):440–453

    Article  CAS  PubMed  Google Scholar 

  20. Piccinotti S, Whelan SP (2016) Rabies internalizes into primary peripheral neurons via clathrin coated pits and requires fusion at the cell body. PLoS Pathog 12(7):e1005753. https://doi.org/10.1371/journal.ppat.1005753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Albertini AAV, Baquero E, Ferlin A, Gaudin Y (2012) Molecular and cellular aspects of rhabdovirus entry. Viruses 4(1):117–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Albertini AA, Ruigrok RW, Blondel D (2011) Rabies virus transcription and replication. Adv Virus Res 79:1–22. https://doi.org/10.1016/B978-0-12-387040-7.00001-9

    Article  CAS  PubMed  Google Scholar 

  23. Blumberg BM, Leppert M, Kolakofsky D (1981) Interaction of VSV leader RNA and nucleocapsid protein may control VSV genome replication. Cell 23(3):837–845

    Article  CAS  PubMed  Google Scholar 

  24. Albertini AA, Wernimont AK, Muziol T, Ravelli RB, Clapier CR, Schoehn G, Weissenhorn W, Ruigrok RW (2006) Crystal structure of the rabies virus nucleoprotein-RNA complex. Science 313(5785):360–363. https://doi.org/10.1126/science.1125280

    Article  CAS  PubMed  Google Scholar 

  25. Emerson SU, Wagner RR (1973) L protein requirement for in vitro RNA synthesis by vesicular stomatitis virus. J Virol 12(6):1325–1335

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Hercyk N, Horikami SM, Moyer SA (1988) The vesicular stomatitis virus L protein possesses the mRNA methyltransferase activities. Virology 163(1):222–225

    Article  CAS  PubMed  Google Scholar 

  27. Ogino T, Banerjee AK (2007) Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus. Mol Cell 25(1):85–97. https://doi.org/10.1016/j.molcel.2006.11.013

    Article  CAS  PubMed  Google Scholar 

  28. Hunt DM, Smith EF, Buckley DW (1984) Aberrant polyadenylation by a vesicular stomatitis virus mutant is due to an altered L protein. J Virol 52(2):515–521

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Liang B, Li Z, Jenni S, Rahmeh AA, Morin BM, Grant T, Grigorieff N, Harrison SC, Whelan SPJ (2015) Structure of the L protein of vesicular stomatitis virus from electron cryomicroscopy. Cell 162(2):314–327. https://doi.org/10.1016/j.cell.2015.06.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gerard FC, Ribeiro Ede A Jr, Leyrat C, Ivanov I, Blondel D, Longhi S, Ruigrok RW, Jamin M (2009) Modular organization of rabies virus phosphoprotein. J Mol Biol 388(5):978–996. https://doi.org/10.1016/j.jmb.2009.03.061

    Article  CAS  PubMed  Google Scholar 

  31. Gupta AK, Blondel D, Choudhary S, Banerjee AK (2000) The phosphoprotein of rabies virus is phosphorylated by a unique cellular protein kinase and specific isomers of protein kinase C. J Virol 74(1):91–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gigant B, Iseni F, Gaudin Y, Knossow M, Blondel D (2000) Neither phosphorylation nor the amino-terminal part of rabies virus phosphoprotein is required for its oligomerization. J Gen Virol 81. (Pt 7:1757–1761. https://doi.org/10.1099/0022-1317-81-7-1757

    Article  CAS  PubMed  Google Scholar 

  33. Castel G, Chteoui M, Caignard G, Prehaud C, Mehouas S, Real E, Jallet C, Jacob Y, Ruigrok RW, Tordo N (2009) Peptides that mimic the amino-terminal end of the rabies virus phosphoprotein have antiviral activity. J Virol 83(20):10808–10820. https://doi.org/10.1128/JVI.00977-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chenik M, Schnell M, Conzelmann KK, Blondel D (1998) Mapping the interacting domains between the rabies virus polymerase and phosphoprotein. J Virol 72(3):1925–1930

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Mavrakis M, Iseni F, Mazza C, Schoehn G, Ebel C, Gentzel M, Franz T, Ruigrok RW (2003) Isolation and characterisation of the rabies virus N degrees-P complex produced in insect cells. Virology 305(2):406–414

    Article  CAS  PubMed  Google Scholar 

  36. Leyrat C, Yabukarski F, Tarbouriech N, Ribeiro EA Jr, Jensen MR, Blackledge M, Ruigrok RW, Jamin M (2011) Structure of the vesicular stomatitis virus N(0)-P complex. PLoS Pathog 7(9):e1002248. https://doi.org/10.1371/journal.ppat.1002248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ivanov I, Crépin T, Jamin M, Ruigrok RW (2010) Structure of the dimerization domain of the rabies virus phosphoprotein. J Virol 84(7):3707–3710. https://doi.org/10.1128/JVI.02557-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mavrakis M, McCarthy AA, Roche S, Blondel D, Ruigrok RW (2004) Structure and function of the C-terminal domain of the polymerase cofactor of rabies virus. J Mol Biol 343(4):819–831. https://doi.org/10.1016/j.jmb.2004.08.071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ribeiro Ede A Jr, Leyrat C, Gerard FC, Albertini AA, Falk C, Ruigrok RW, Jamin M (2009) Binding of rabies virus polymerase cofactor to recombinant circular nucleoprotein-RNA complexes. J Mol Biol 394(3):558–575. https://doi.org/10.1016/j.jmb.2009.09.042

    Article  CAS  PubMed  Google Scholar 

  40. Jacob Y, Real E, Tordo N (2001) Functional interaction map of lyssavirus phosphoprotein: identification of the minimal transcription domains. J Virol 75(20):9613–9622. https://doi.org/10.1128/JVI.75.20.9613-9622.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Green TJ, Luo M (2009) Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P. Proc Natl Acad Sci U S A 106(28):11713–11718. https://doi.org/10.1073/pnas.0903228106

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chelbi-Alix MK, Vidy A, El Bougrini J, Blondel D (2006) Rabies viral mechanisms to escape the IFN system: the viral protein P interferes with IRF-3, Stat1, and PML nuclear bodies. J Interf Cytokine Res 26(5):271–280. https://doi.org/10.1089/jir.2006.26.271

    Article  CAS  Google Scholar 

  43. Vidy A, Chelbi-Alix M, Blondel D (2005) Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways. J Virol 79(22):14411–14420. https://doi.org/10.1128/JVI.79.22.14411-14420.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vidy A, El Bougrini J, Chelbi-Alix MK, Blondel D (2007) The nucleocytoplasmic rabies virus P protein counteracts interferon signaling by inhibiting both nuclear accumulation and DNA binding of STAT1. J Virol 81(8):4255–4263. https://doi.org/10.1128/JVI.01930-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Blondel D, Regad T, Poisson N, Pavie B, Harper F, Pandolfi PP, De The H, Chelbi-Alix MK (2002) Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies. Oncogene 21(52):7957–7970. https://doi.org/10.1038/sj.onc.1205931

    Article  CAS  PubMed  Google Scholar 

  46. Blondel D, Kheddache S, Lahaye X, Dianoux L, Chelbi-Alix MK (2010) Resistance to rabies virus infection conferred by the PMLIV isoform. J Virol 84(20):10719–10726. https://doi.org/10.1128/JVI.01286-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 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(12):7673–7681. https://doi.org/10.1128/JVI.79.12.7673-7681.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jacob Y, Badrane H, Ceccaldi PE, Tordo N (2000) Cytoplasmic dynein LC8 interacts with lyssavirus phosphoprotein. J Virol 74(21):10217–10222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Poisson N, Real E, Gaudin Y, Vaney MC, King S, Jacob Y, Tordo N, Blondel D (2001) Molecular basis for the interaction between rabies virus phosphoprotein P and the dynein light chain LC8: dissociation of dynein-binding properties and transcriptional functionality of P. J Gen Virol 82. (Pt 11:2691–2696. https://doi.org/10.1099/0022-1317-82-11-2691

    Article  CAS  PubMed  Google Scholar 

  50. Raux H, Flamand A, Blondel D (2000) Interaction of the rabies virus P protein with the LC8 dynein light chain. J Virol 74(21):10212–10216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fouquet B, Nikolic J, Larrous F, Bourhy H, Wirblich C, Lagaudriere-Gesbert C, Blondel D (2015) Focal adhesion kinase is involved in rabies virus infection through its interaction with viral phosphoprotein P. J Virol 89(3):1640–1651. https://doi.org/10.1128/JVI.02602-14

    Article  CAS  PubMed  Google Scholar 

  52. Oksayan S, Nikolic J, David CT, Blondel D, Jans DA, Moseley GW (2015) Identification of a role for nucleolin in rabies virus infection. J Virol 89(3):1939–1943. https://doi.org/10.1128/JVI.03320-14

    Article  CAS  PubMed  Google Scholar 

  53. Tan GS, Preuss MA, Williams JC, Schnell MJ (2007) The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription. Proc Natl Acad Sci U S A 104(17):7229–7234. https://doi.org/10.1073/pnas.0701397104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kristensson K, Dastur DK, Manghani DK, Tsiang H, Bentivoglio M (1996) Rabies: interactions between neurons and viruses. A review of the history of Negri inclusion bodies. Neuropathol Appl Neurobiol 22(3):179–187

    Article  CAS  PubMed  Google Scholar 

  55. Nikolic J, Le Bars R, Lama Z, Scrima N, Lagaudriere-Gesbert C, Gaudin Y, Blondel D (2017) Negri bodies are viral factories with properties of liquid organelles. Nat Commun 8(1):58. https://doi.org/10.1038/s41467-017-00102-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Matsumoto S, Schneider LG, Kawai A, Yonezawa T (1974) Further studies on the replication of rabies and rabies-like viruses in organized cultures of mammalian neural tissues. J Virol 14(4):981–996

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Finke S, Brzozka K, Conzelmann KK (2004) Tracking fluorescence-labeled rabies virus: enhanced green fluorescent protein-tagged phosphoprotein P supports virus gene expression and formation of infectious particles. J Virol 78(22):12333–12343. https://doi.org/10.1128/JVI.78.22.12333-12343.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lahaye X, Vidy A, Fouquet B, Blondel D (2012) Hsp70 protein positively regulates rabies virus infection. J Virol 86(9):4743–4751. https://doi.org/10.1128/JVI.06501-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhang J, Wu X, Zan J, Wu Y, Ye C, Ruan X, Zhou J (2013a) Cellular chaperonin CCTgamma contributes to rabies virus replication during infection. J Virol 87(13):7608–7621. https://doi.org/10.1128/JVI.03186-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang J, Ye C, Ruan X, Zan J, Xu Y, Liao M, Zhou J (2014) The chaperonin CCTalpha is required for efficient transcription and replication of rabies virus. Microbiol Immunol 58(10):590–599. https://doi.org/10.1111/1348-0421.12186

    Article  CAS  PubMed  Google Scholar 

  61. Shin T, Weinstock D, Castro MD, Hamir AN, Wampler T, Walter M, Kim HY, Acland H (2004) Immunohistochemical localization of endothelial and inducible nitric oxide synthase within neurons of cattle with rabies. J Vet Med Sci 66(5):539–541

    Article  PubMed  Google Scholar 

  62. Pollin R, Granzow H, Kollner B, Conzelmann KK, Finke S (2013) Membrane and inclusion body targeting of lyssavirus matrix proteins. Cell Microbiol 15(2):200–212. https://doi.org/10.1111/cmi.12037

    Article  CAS  PubMed  Google Scholar 

  63. Banani SF, Lee HO, Hyman AA, Rosen MK (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18(5):285–298. https://doi.org/10.1038/nrm.2017.7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Brangwynne CP, Eckmann CR, Courson DS, Rybarska A, Hoege C, Gharakhani J, Julicher F, Hyman AA (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324(5935):1729–1732. https://doi.org/10.1126/science.1172046

    Article  CAS  PubMed  Google Scholar 

  65. Courchaine EM, Lu A, Neugebauer KM (2016) Droplet organelles? EMBO J 35(15):1603–1612. https://doi.org/10.15252/embj.201593517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Uversky VN (2017) Intrinsically disordered proteins in overcrowded milieu: membrane-less organelles, phase separation, and intrinsic disorder. Curr Opin Struct Biol 44:18–30. https://doi.org/10.1016/j.sbi.2016.10.015

    Article  CAS  PubMed  Google Scholar 

  67. Handwerger KE, Cordero JA, Gall JG (2005) Cajal bodies, nucleoli, and speckles in the Xenopus oocyte nucleus have a low-density, sponge-like structure. Mol Biol Cell 16(1):202–211. https://doi.org/10.1091/mbc.E04-08-0742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Brangwynne CP, Mitchison TJ, Hyman AA (2011) Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc Natl Acad Sci U S A 108(11):4334–4339. https://doi.org/10.1073/pnas.1017150108

    Article  PubMed  PubMed Central  Google Scholar 

  69. Feric M, Vaidya N, Harmon TS, Mitrea DM, Zhu L, Richardson TM, Kriwacki RW, Pappu RV, Brangwynne CP (2016) Coexisting liquid phases underlie nucleolar subcompartments. Cell 165(7):1686–1697. https://doi.org/10.1016/j.cell.2016.04.047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Marzahn MR, Marada S, Lee J, Nourse A, Kenrick S, Zhao H, Ben-Nissan G, Kolaitis RM, Peters JL, Pounds S, Errington WJ, Prive GG, Taylor JP, Sharon M, Schuck P, Ogden SK, Mittag T (2016) Higher-order oligomerization promotes localization of SPOP to liquid nuclear speckles. EMBO J 35(12):1254–1275. https://doi.org/10.15252/embj.201593169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jain S, Wheeler JR, Walters RW, Agrawal A, Barsic A, Parker R (2016) ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164(3):487–498. https://doi.org/10.1016/j.cell.2015.12.038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 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(10):e1005942. https://doi.org/10.1371/journal.ppat.1005942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Nielsen FC, Hansen HT, Christiansen J (2016) RNA assemblages orchestrate complex cellular processes. BioEssays 38(7):674–681. https://doi.org/10.1002/bies.201500175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Berry J, Weber SC, Vaidya N, Haataja M, Brangwynne CP (2015) RNA transcription modulates phase transition-driven nuclear body assembly. Proc Natl Acad Sci U S A 112(38):E5237–E5245. https://doi.org/10.1073/pnas.1509317112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Elbaum-Garfinkle S, Kim Y, Szczepaniak K, Chen CC, Eckmann CR, Myong S, Brangwynne CP (2015) The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. Proc Natl Acad Sci U S A 112(23):7189–7194. https://doi.org/10.1073/pnas.1504822112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nott TJ, Petsalaki E, Farber P, Jervis D, Fussner E, Plochowietz A, Craggs TD, Bazett-Jones DP, Pawson T, Forman-Kay JD, Baldwin AJ (2015) Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol Cell 57(5):936–947. https://doi.org/10.1016/j.molcel.2015.01.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Tompa P, Fuxreiter M (2008) Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem Sci 33(1):2–8. https://doi.org/10.1016/j.tibs.2007.10.003

    Article  CAS  PubMed  Google Scholar 

  78. Schudt G, Kolesnikova L, Dolnik O, Sodeik B, Becker S (2013) Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances. Proc Natl Acad Sci U S A 110(35):14402–14407. https://doi.org/10.1073/pnas.1307681110

    Article  PubMed  PubMed Central  Google Scholar 

  79. Derdowski A, Peters TR, Glover N, Qian R, Utley TJ, Burnett A, Williams JV, Spearman P, Crowe JE Jr (2008) Human metapneumovirus nucleoprotein and phosphoprotein interact and provide the minimal requirements for inclusion body formation. J Gen Virol 89(Pt 11):2698–2708. https://doi.org/10.1099/vir.0.2008/004051-0

    Article  CAS  PubMed  Google Scholar 

  80. 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. (Pt 12:3525–3539. https://doi.org/10.1099/0022-1317-75-12-3525

    Article  CAS  PubMed  Google Scholar 

  81. Zhang S, Chen L, Zhang G, Yan Q, Yang X, Ding B, Tang Q, Sun S, Hu Z, Chen M (2013b) An amino acid of human parainfluenza virus type 3 nucleoprotein is critical for template function and cytoplasmic inclusion body formation. J Virol 87(22):12457–12470. https://doi.org/10.1128/JVI.01565-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Charlier CM, Wu YJ, Allart S, Malnou CE, Schwemmle M, Gonzalez-Dunia D (2013) Analysis of borna disease virus trafficking in live infected cells by using a virus encoding a tetracysteine-tagged p protein. J Virol 87(22):12339–12348. https://doi.org/10.1128/JVI.01127-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wichgers Schreur PJ, Kortekaas J (2016) Single-molecule FISH reveals non-selective packaging of rift valley fever virus genome segments. PLoS Pathog 12(8):e1005800. https://doi.org/10.1371/journal.ppat.1005800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Chaikeeratisak V, Nguyen K, Khanna K, Brilot AF, Erb ML, Coker JK, Vavilina A, Newton GL, Buschauer R, Pogliano K, Villa E, Agard DA, Pogliano J (2017) Assembly of a nucleus-like structure during viral replication in bacteria. Science 355(6321):194–197. https://doi.org/10.1126/science.aal2130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Oh SW, Onomoto K, Wakimoto M, Onoguchi K, Ishidate F, Fujiwara T, Yoneyama M, Kato H, Fujita T (2016) Leader-containing uncapped viral transcript activates RIG-I in antiviral stress granules. PLoS Pathog 12(2):e1005444. https://doi.org/10.1371/journal.ppat.1005444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dinh PX, Beura LK, Das PB, Panda D, Das A, Pattnaik AK (2013) Induction of stress granule-like structures in vesicular stomatitis virus-infected cells. J Virol 87(1):372–383. https://doi.org/10.1128/JVI.02305-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the CNRS and by a grant from the Fondation pour la Recherche Médicale (FRM DEQ20120323711) to Y.G.

Author information

Authors and Affiliations

  1. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette cedex, France

    Jovan Nikolic, Cécile Lagaudrière-Gesbert, Nathalie Scrima, Danielle Blondel & Yves Gaudin

Authors
  1. Jovan Nikolic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cécile Lagaudrière-Gesbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nathalie Scrima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danielle Blondel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yves Gaudin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Danielle Blondel or Yves Gaudin .

Editor information

Editors and Affiliations

  1. Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

    Urs F. Greber

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nikolic, J., Lagaudrière-Gesbert, C., Scrima, N., Blondel, D., Gaudin, Y. (2019). Structure and Function of Negri Bodies. In: Greber, U. (eds) Physical Virology. Advances in Experimental Medicine and Biology, vol 1215. Springer, Cham. https://doi.org/10.1007/978-3-030-14741-9_6

Download citation

Publish with us

Policies and ethics

Search

Navigation