Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication

20 pages, 10 figures, 1 table

Detalles Bibliográficos
Autores: Romero Jódar, Alejandro, Figueras Huerta, Antonio, Novoa, Beatriz
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/390792
Acceso en línea:http://hdl.handle.net/10261/390792
Access Level:acceso abierto
Palabra clave:Viral infection
SVCV
Endoplasmic reticulum (ER)
Unfolded protein response (UPR)
Antiviral activity
Viral replication
Immune response
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spelling Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replicationRomero Jódar, AlejandroFigueras Huerta, AntonioNovoa, BeatrizViral infectionSVCVEndoplasmic reticulum (ER)Unfolded protein response (UPR)Antiviral activityViral replicationImmune response20 pages, 10 figures, 1 table[Introduction] The spring viraemia of carp virus (SVCV) poses a significant threat to global aquaculture, yet effective antiviral drugs and vaccines remain unavailable. Understanding the interplay between host-pathogen interactions and SVCV replication is crucial for devising preventive strategies. [Methods] ZF4 cells were exposed to UV-inactivated SVCV or live SVCV at different multiplicities of infection, and the modulation of the unfolded protein response (UPR) was assayed by qPCR at different times. Moreover, ZF4 cells were treated with several UPR modulators to investigate their effect on viral replication. The UPR was also modulated in vivo in zebrafish larvae, and its impact on the survival against SVCV infection was evaluated. [Results and conclusions] This study reveals how SVCV exploits the host’s UPR to facilitate its replication. SVCV targets the immunoglobulin heavy chain-binding protein (BiP) and the activating transcription factor 4 (ATF4) during early infection to enhance viral RNA synthesis and translation. At later stages, activation of the BiP, the PKR-like ER kinase (PERK), and the inositol-requiring enzyme 1 alpha (IRE1α) pathways supports the release of viral progeny and induces cellular processes, including immune responses and apoptotic cell death. Furthermore, the data demonstrate that modulating UPR pathways, particularly ATF6 and PERK, significantly affect viral replication, providing a novel avenue for antiviral drug development. Preliminary in vivo studies suggest the feasibility of chemically modulating the UPR to combat SVCV, though optimizing administration conditions to maximize efficacy while minimizing side effects warrants further investigation. These findings offer critical insights into the molecular mechanisms underlying SVCV pathogenesis and highlight promising targets for therapeutic interventionOur laboratory is funded by projects PID2020-119532RB-I00 and PID2023-148810OB-C21 from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU), the Agencia Estatal de Investigación (AEI) and the European Regional Development Fund (ERDF) (MCIU/AEI/10.13039/501100011033/FEDER, UE), MetDisFish from Ministerio de Agricultura, Pesca y Alimentación (MAPA) and European Maritime, Fisheries and Aquaculture Fund (EMFAF) (Spain) and IN607B 2019/01 from Conselleria de Economia, Emprego e Industria (GAIN), Xunta de Galicia (Spain)Peer reviewedFrontiers MediaMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionMinisterio de Agricultura, Pesca y Alimentación (España)European Maritime, Fisheries and Aquaculture FundXunta de GaliciaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/390792reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119532RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-148810OB-C21The underlying dataset has been published as supplementary material of the article in the publishers platform at DOI https://doi.org/10.3389/fimmu.2025.1576758https://doi.org/10.3389/fimmu.2025.1576758Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3907922026-05-22T06:33:51Z
dc.title.none.fl_str_mv Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
title Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
spellingShingle Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
Romero Jódar, Alejandro
Viral infection
SVCV
Endoplasmic reticulum (ER)
Unfolded protein response (UPR)
Antiviral activity
Viral replication
Immune response
title_short Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
title_full Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
title_fullStr Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
title_full_unstemmed Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
title_sort Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication
dc.creator.none.fl_str_mv Romero Jódar, Alejandro
Figueras Huerta, Antonio
Novoa, Beatriz
author Romero Jódar, Alejandro
author_facet Romero Jódar, Alejandro
Figueras Huerta, Antonio
Novoa, Beatriz
author_role author
author2 Figueras Huerta, Antonio
Novoa, Beatriz
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Commission
Ministerio de Agricultura, Pesca y Alimentación (España)
European Maritime, Fisheries and Aquaculture Fund
Xunta de Galicia
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Viral infection
SVCV
Endoplasmic reticulum (ER)
Unfolded protein response (UPR)
Antiviral activity
Viral replication
Immune response
topic Viral infection
SVCV
Endoplasmic reticulum (ER)
Unfolded protein response (UPR)
Antiviral activity
Viral replication
Immune response
description 20 pages, 10 figures, 1 table
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/390792
url http://hdl.handle.net/10261/390792
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119532RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-148810OB-C21
The underlying dataset has been published as supplementary material of the article in the publishers platform at DOI https://doi.org/10.3389/fimmu.2025.1576758
https://doi.org/10.3389/fimmu.2025.1576758
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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