How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?

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 re...

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Main Authors: Akatsuki Saito, Maya Shofa, Hirotaka Ode, Maho Yumiya, Junki Hirano, Toru Okamoto, Shige H. Yoshimura
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/8/1479
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author Akatsuki Saito
Maya Shofa
Hirotaka Ode
Maho Yumiya
Junki Hirano
Toru Okamoto
Shige H. Yoshimura
author_facet Akatsuki Saito
Maya Shofa
Hirotaka Ode
Maho Yumiya
Junki Hirano
Toru Okamoto
Shige H. Yoshimura
author_sort Akatsuki Saito
collection DOAJ
description 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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spelling doaj.art-63a1d4e115c246d9897a2c0d8b105c392023-11-22T10:09:56ZengMDPI AGViruses1999-49152021-07-01138147910.3390/v13081479How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?Akatsuki Saito0Maya Shofa1Hirotaka Ode2Maho Yumiya3Junki Hirano4Toru Okamoto5Shige H. Yoshimura6Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, JapanDepartment of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, JapanClinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, JapanResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanLaboratory of Plasma Membrane and Nuclear Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, JapanViral 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.https://www.mdpi.com/1999-4915/13/8/1479flavivirusliquid–liquid phase separationdisordered proteinpathogenicity
spellingShingle Akatsuki Saito
Maya Shofa
Hirotaka Ode
Maho Yumiya
Junki Hirano
Toru Okamoto
Shige H. Yoshimura
How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?
Viruses
flavivirus
liquid–liquid phase separation
disordered protein
pathogenicity
title How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?
title_full How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?
title_fullStr How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?
title_full_unstemmed How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?
title_short How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?
title_sort how do flaviviruses hijack host cell functions by phase separation
topic flavivirus
liquid–liquid phase separation
disordered protein
pathogenicity
url https://www.mdpi.com/1999-4915/13/8/1479
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