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How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?

Authors
  • Saito, Akatsuki1, 2, 3
  • Shofa, Maya1, 3
  • Ode, Hirotaka4
  • Yumiya, Maho5
  • Hirano, Junki5
  • Okamoto, Toru5, 6
  • Yoshimura, Shige H7
  • 1 Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan. , (Japan)
  • 2 Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan. , (Japan)
  • 3 Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan. , (Japan)
  • 4 Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Japan. , (Japan)
  • 5 Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. , (Japan)
  • 6 Center for Infectious Diseases Education and Research, Osaka University, Osaka 565-0871, Japan. , (Japan)
  • 7 Laboratory of Plasma Membrane and Nuclear Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan. , (Japan)
Type
Published Article
Journal
Viruses
Publisher
MDPI AG
Publication Date
Jul 28, 2021
Volume
13
Issue
8
Identifiers
DOI: 10.3390/v13081479
PMID: 34452345
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Viral proteins interact with different sets of host cell components throughout the viral life cycle and are known to localize to the intracellular membraneless organelles (MLOs) of the host cell, where formation/dissolution is regulated by phase separation of intrinsically disordered proteins and regions (IDPs/IDRs). Viral proteins are rich in IDRs, implying that viruses utilize IDRs to regulate phase separation of the host cell organelles and augment replication by commandeering the functions of the organelles and/or sneaking into the organelles to evade the host immune response. This review aims to integrate current knowledge of the structural properties and intracellular localizations of viral IDPs to understand viral strategies in the host cell. First, the properties of viral IDRs are reviewed and similarities and differences with those of eukaryotes are described. The higher IDR content in viruses with smaller genomes suggests that IDRs are essential characteristics of viral proteins. Then, the interactions of the IDRs of flaviviruses with the MLOs of the host cell are investigated with emphasis on the viral proteins localized in the nucleoli and stress granules. Finally, the possible roles of viral IDRs in regulation of the phase separation of organelles and future possibilities for antiviral drug development are discussed.

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