Defining basic rules for hardening influenza A virus liquid condensates

In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of...

Full description

Bibliographic Details
Main Authors: Temitope Akhigbe Etibor, Silvia Vale-Costa, Sindhuja Sridharan, Daniela Brás, Isabelle Becher, Victor Hugo Mello, Filipe Ferreira, Marta Alenquer, Mikhail M Savitski, Maria-João Amorim
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-04-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/85182
_version_ 1797834999499587584
author Temitope Akhigbe Etibor
Silvia Vale-Costa
Sindhuja Sridharan
Daniela Brás
Isabelle Becher
Victor Hugo Mello
Filipe Ferreira
Marta Alenquer
Mikhail M Savitski
Maria-João Amorim
author_facet Temitope Akhigbe Etibor
Silvia Vale-Costa
Sindhuja Sridharan
Daniela Brás
Isabelle Becher
Victor Hugo Mello
Filipe Ferreira
Marta Alenquer
Mikhail M Savitski
Maria-João Amorim
author_sort Temitope Akhigbe Etibor
collection DOAJ
description In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of biological condensates and that material properties can be tuned by several factors including temperature, concentration, and valency. It is, however, unclear if some factors are more efficient than others at regulating their behaviour. Viral infections are good systems to address this question as they form condensates de novo as part of their replication programmes. Here, we used influenza A virus (IAV) liquid cytosolic condensates, AKA viral inclusions, to provide a proof of concept that liquid condensate hardening via changes in the valency of its components is more efficient than altering their concentration or the temperature of the cell. Liquid IAV inclusions may be hardened by targeting vRNP (viral ribonucleoprotein) interactions via the known NP (nucleoprotein) oligomerising molecule, nucleozin, both in vitro and in vivo without affecting host proteome abundance nor solubility. This study is a starting point for understanding how to pharmacologically modulate the material properties of IAV inclusions and may offer opportunities for alternative antiviral strategies.
first_indexed 2024-04-09T14:47:36Z
format Article
id doaj.art-3f7caaf707fb473f862bd3c0a076c3a3
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-04-09T14:47:36Z
publishDate 2023-04-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-3f7caaf707fb473f862bd3c0a076c3a32023-05-02T12:03:46ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.85182Defining basic rules for hardening influenza A virus liquid condensatesTemitope Akhigbe Etibor0https://orcid.org/0000-0002-9024-4310Silvia Vale-Costa1Sindhuja Sridharan2Daniela Brás3Isabelle Becher4https://orcid.org/0000-0001-7170-2235Victor Hugo Mello5Filipe Ferreira6Marta Alenquer7https://orcid.org/0000-0003-3062-1222Mikhail M Savitski8https://orcid.org/0000-0003-2011-9247Maria-João Amorim9https://orcid.org/0000-0002-4129-6659Cell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalEuropean Molecular Biology Laboratory, Heidelberg, GermanyCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalEuropean Molecular Biology Laboratory, Heidelberg, GermanyCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal; Cell Biology of Viral Infection Lab, Universidade Católica Portuguesa, Católica Medical School, Católica Biomedical Research Centre, Lisbon, PortugalEuropean Molecular Biology Laboratory, Heidelberg, GermanyCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal; Cell Biology of Viral Infection Lab, Universidade Católica Portuguesa, Católica Medical School, Católica Biomedical Research Centre, Lisbon, PortugalIn biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of biological condensates and that material properties can be tuned by several factors including temperature, concentration, and valency. It is, however, unclear if some factors are more efficient than others at regulating their behaviour. Viral infections are good systems to address this question as they form condensates de novo as part of their replication programmes. Here, we used influenza A virus (IAV) liquid cytosolic condensates, AKA viral inclusions, to provide a proof of concept that liquid condensate hardening via changes in the valency of its components is more efficient than altering their concentration or the temperature of the cell. Liquid IAV inclusions may be hardened by targeting vRNP (viral ribonucleoprotein) interactions via the known NP (nucleoprotein) oligomerising molecule, nucleozin, both in vitro and in vivo without affecting host proteome abundance nor solubility. This study is a starting point for understanding how to pharmacologically modulate the material properties of IAV inclusions and may offer opportunities for alternative antiviral strategies.https://elifesciences.org/articles/85182influenza A virusbiomolecular condensatesviral inclusionsphase transitionsproteome-wide solubility
spellingShingle Temitope Akhigbe Etibor
Silvia Vale-Costa
Sindhuja Sridharan
Daniela Brás
Isabelle Becher
Victor Hugo Mello
Filipe Ferreira
Marta Alenquer
Mikhail M Savitski
Maria-João Amorim
Defining basic rules for hardening influenza A virus liquid condensates
eLife
influenza A virus
biomolecular condensates
viral inclusions
phase transitions
proteome-wide solubility
title Defining basic rules for hardening influenza A virus liquid condensates
title_full Defining basic rules for hardening influenza A virus liquid condensates
title_fullStr Defining basic rules for hardening influenza A virus liquid condensates
title_full_unstemmed Defining basic rules for hardening influenza A virus liquid condensates
title_short Defining basic rules for hardening influenza A virus liquid condensates
title_sort defining basic rules for hardening influenza a virus liquid condensates
topic influenza A virus
biomolecular condensates
viral inclusions
phase transitions
proteome-wide solubility
url https://elifesciences.org/articles/85182
work_keys_str_mv AT temitopeakhigbeetibor definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT silviavalecosta definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT sindhujasridharan definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT danielabras definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT isabellebecher definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT victorhugomello definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT filipeferreira definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT martaalenquer definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT mikhailmsavitski definingbasicrulesforhardeninginfluenzaavirusliquidcondensates
AT mariajoaoamorim definingbasicrulesforhardeninginfluenzaavirusliquidcondensates