Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication

Usutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient data on the virus or host cel...

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Detalhes bibliográficos
Autores: Albentosa González, Laura, Sabariegos Jareño, María del Rosario, Arias Esteban, Armando, Clemente Casares, Pilar, Mas López, Antonio
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/45870
Acesso em linha:https://hdl.handle.net/10578/45870
Access Level:acceso abierto
Palavra-chave:Host factors
Inhibitors
NS5
PI3K/Akt/mTOR pathway
Replicase
RNA-dependent RNA-polymerase
USUV
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spelling Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral ReplicationAlbentosa González, LauraSabariegos Jareño, María del RosarioArias Esteban, ArmandoClemente Casares, PilarMas López, AntonioHost factorsInhibitorsNS5PI3K/Akt/mTOR pathwayReplicaseRNA-dependent RNA-polymeraseUSUVUsutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient data on the virus or host cell targets for infection control. In this work we have investigated whether the cellular kinase Akt and USUV polymerase NS5 interact and co-localize in a cell. To this aim, we performed co-immunoprecipitation (Co-IP) assays, followed by confocal microscopy analyses. We further tested whether NS5 is a phosphorylation substrate of Akt in vitro. Finally, to examine its role in viral replication, we chemically silenced Akt with three inhibitors (MK-2206, honokiol and ipatasertib). We found that both proteins are localized (confocal) and pulled down (Co-IP) together when expressed in different cell lines, supporting the fact that they are interacting partners. This possibility was further sustained by data showing that NS5 is phosphorylated by Akt. Treatment of USUV-infected cells with Akt-specific inhibitors led to decreases in virus titers (>10-fold). Our results suggest an important role for Akt in virus replication and stimulate further investigations to examine the PI3K/Akt/mTOR pathway as an antiviral target.MDPI202520252021info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/45870reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésSAF2016-80451-PPID2019-106068GB-I00GI20163501GI201741002019-GRIN-27080info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/458702026-05-27T07:36:41Z
dc.title.none.fl_str_mv Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
title Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
spellingShingle Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
Albentosa González, Laura
Host factors
Inhibitors
NS5
PI3K/Akt/mTOR pathway
Replicase
RNA-dependent RNA-polymerase
USUV
title_short Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
title_full Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
title_fullStr Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
title_full_unstemmed Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
title_sort Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
dc.creator.none.fl_str_mv Albentosa González, Laura
Sabariegos Jareño, María del Rosario
Arias Esteban, Armando
Clemente Casares, Pilar
Mas López, Antonio
author Albentosa González, Laura
author_facet Albentosa González, Laura
Sabariegos Jareño, María del Rosario
Arias Esteban, Armando
Clemente Casares, Pilar
Mas López, Antonio
author_role author
author2 Sabariegos Jareño, María del Rosario
Arias Esteban, Armando
Clemente Casares, Pilar
Mas López, Antonio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Host factors
Inhibitors
NS5
PI3K/Akt/mTOR pathway
Replicase
RNA-dependent RNA-polymerase
USUV
topic Host factors
Inhibitors
NS5
PI3K/Akt/mTOR pathway
Replicase
RNA-dependent RNA-polymerase
USUV
description Usutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient data on the virus or host cell targets for infection control. In this work we have investigated whether the cellular kinase Akt and USUV polymerase NS5 interact and co-localize in a cell. To this aim, we performed co-immunoprecipitation (Co-IP) assays, followed by confocal microscopy analyses. We further tested whether NS5 is a phosphorylation substrate of Akt in vitro. Finally, to examine its role in viral replication, we chemically silenced Akt with three inhibitors (MK-2206, honokiol and ipatasertib). We found that both proteins are localized (confocal) and pulled down (Co-IP) together when expressed in different cell lines, supporting the fact that they are interacting partners. This possibility was further sustained by data showing that NS5 is phosphorylated by Akt. Treatment of USUV-infected cells with Akt-specific inhibitors led to decreases in virus titers (>10-fold). Our results suggest an important role for Akt in virus replication and stimulate further investigations to examine the PI3K/Akt/mTOR pathway as an antiviral target.
publishDate 2021
dc.date.none.fl_str_mv 2021
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/45870
url https://hdl.handle.net/10578/45870
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SAF2016-80451-P
PID2019-106068GB-I00
GI20163501
GI20174100
2019-GRIN-27080
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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