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How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?

Akatsuki Saito1,2,3, Maya Shofa1,3, Hirotaka Ode4

  • 1Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.

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Viruses use intrinsically disordered regions (IDRs) in their proteins to hijack host cell membraneless organelles (MLOs). This viral strategy aids replication and immune evasion by manipulating MLO phase separation.

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disordered proteinflavivirusliquid–liquid phase separationpathogenicity

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Area of Science:

  • Virology
  • Structural Biology
  • Cell Biology

Background:

  • Viral proteins interact with host cell components, localizing to membraneless organelles (MLOs).
  • MLO formation/dissolution is governed by phase separation of intrinsically disordered proteins/regions (IDPs/IDRs).
  • Viral proteins exhibit a high content of IDRs, suggesting their crucial role in viral strategies.

Purpose of the Study:

  • To review and integrate knowledge on the structural properties and intracellular localizations of viral IDPs.
  • To understand how viruses utilize IDRs to manipulate host cell MLOs for replication and immune evasion.
  • To explore the potential of viral IDRs in regulating MLO phase separation and for antiviral drug development.

Main Methods:

  • Review of existing literature on viral IDPs and their interactions with host MLOs.
  • Analysis of structural properties and intracellular localization patterns of viral IDPs.
  • Emphasis on flaviviruses and their IDPs' interactions with nucleoli and stress granules.

Main Results:

  • Viral proteins are rich in IDRs, with higher content in viruses possessing smaller genomes.
  • Viral IDRs are implicated in regulating the phase separation of host cell MLOs.
  • Specific viral proteins localize to host nucleoli and stress granules, suggesting commandeering of these MLOs.

Conclusions:

  • Viral IDRs are essential for viral strategies, enabling manipulation of host MLOs.
  • Understanding viral IDR functions offers potential for novel antiviral drug development targeting MLO phase separation.
  • Viruses leverage IDRs to enhance replication and evade host immune responses by hijacking cellular machinery.