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Structure and Function of Negri Bodies.

Jovan Nikolic1, Cécile Lagaudrière-Gesbert1, Nathalie Scrima1

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

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Summary
This summary is machine-generated.

Rabies virus forms specialized compartments called Negri bodies (NBs) that function as liquid organelles. These viral factories, crucial for replication, are assembled by viral proteins N and P through liquid phase separation.

Keywords:
Liquid organellesNegri bodiesPhase separationRabies virusViral factory

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Area of Science:

  • Virology
  • Cell Biology
  • Biophysics

Background:

  • Viral replication often occurs in specialized intracellular compartments known as viral factories.
  • For rabies virus, these factories are Negri bodies (NBs), which are cytoplasmic inclusions where viral RNA synthesis takes place.
  • NBs exhibit characteristics of liquid organelles, including fusion and deformation, suggesting a liquid nature confirmed by FRAP experiments.

Purpose of the Study:

  • To investigate the formation and properties of Negri bodies (NBs) in rabies virus infection.
  • To explore the role of viral proteins N and P in the assembly of these viral factories.
  • To understand the implications of NBs as liquid organelles in viral replication and host-pathogen interactions.

Main Methods:

  • Co-expression of rabies virus nucleoprotein (N) and phosphoprotein (P) to induce cytoplasmic inclusions.
  • Characterization of inclusion body properties, including fusion and deformability.
  • FRAP (Fluorescence Recovery After Photobleaching) experiments to assess the liquid nature of NBs.
  • Literature review on viral factories and liquid organelles within the Mononegavirales order.

Main Results:

  • Co-expression of N and P proteins is sufficient to form inclusions mimicking Negri body properties.
  • Rabies virus nucleoprotein (N) is an RNA-binding protein, and phosphoprotein (P) contains intrinsically disordered domains, similar to proteins forming cellular liquid organelles.
  • Evidence supports that Negri bodies behave as liquid organelles, formed through liquid phase separation.
  • Liquid viral factories likely facilitate the recruitment and concentration of viral proteins.

Conclusions:

  • Negri bodies function as liquid organelles, assembled via phase separation driven by viral proteins N and P.
  • This liquid nature is likely conserved among Mononegavirales, aiding viral protein concentration.
  • The interplay between these liquid viral factories and cellular innate immune sensors warrants further investigation.