I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)

Detalhes bibliográficos
Autor(a) principal: Correia, Silvia
Data de Publicação: 2023
Outros Autores: Moura, Pedro Luís, Ventura, Sónia, Leitão, Alexandre, Parkhouse, Robert Michael Evans
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.5/27882
Resumo: Research Areas: Virology
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spelling I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)African swine fever virusI329L proteinToll-like receptorImmune evasionInnate immunityResearch Areas: VirologyABSTRACT - The African Swine Fever Virus (ASFV) is an economically important, large DNA virus which causes a highly contagious and frequently fatal disease in domestic pigs. Due to the acute nature of the infection and the complexity of the protective porcine anti-ASFV response, there is no accepted vaccine in use. As resistance to ASFV is known to correlate with a robust IFN response, the virus is predicted to have evolved strategies to inhibit innate immunity by modulating the IFN response. The deletion of virus host evasion gene(s) inhibiting IFN is a logical solution to develop an attenuated virus vaccine. One such candidate, the ASFV ORF I329L gene, is highly conserved in pathogenic and non-pathogenic virus isolates and in this study we confirm and extend the conclusion that it has evolved for the inhibition of innate immunity initiated through Toll-like receptors (TLRs). Specifically, the ASFV I329L extracellular (ECD) and intracellular (ICD) domains inhibit TLR signalling by two entirely different mechanisms. Bioinformatics modelling suggests that the ECD inhibits several TLR signalling pathways through a short sequence homologous to the conserved TLR dimerization domain, here termed the putative dimerization domain (PDD). Remarkably, both full length and PDD constructs of I329L were demonstrated to inhibit activation, not only of TLR3, but also TLR4, TLR5, TLR8 and TLR9. Additionally, the demonstration of a weak association of I329L with TLR3 is consistent with the formation of a non-signalling I329L-TLR3 heterodimer, perhaps mediated through the PDD of I329L. Finally, the ICD associates with TRIF, thereby impacting on both TLR3 and TLR4 signalling. Thus, I329L offers potential as a general inhibitor of TLR responses and is a rational candidate for construction and testing of an I329L deletion mutant vaccineMDPIRepositório da Universidade de LisboaCorreia, SilviaMoura, Pedro LuísVentura, SóniaLeitão, AlexandreParkhouse, Robert Michael Evans2023-06-04T20:20:44Z2023-02-052023-02-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.5/27882engCorreia S, Moura PL, Ventura S, Leitão A, Parkhouse RME. 2023. I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV). Viruses,15(2):445. DOI: https://doi.org/10.3390/v1502044510.3390/v150204451999-4915info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-06-11T01:30:34Zoai:www.repository.utl.pt:10400.5/27882Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:00:10.384529Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
title I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
spellingShingle I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
Correia, Silvia
African swine fever virus
I329L protein
Toll-like receptor
Immune evasion
Innate immunity
title_short I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
title_full I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
title_fullStr I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
title_full_unstemmed I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
title_sort I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
author Correia, Silvia
author_facet Correia, Silvia
Moura, Pedro Luís
Ventura, Sónia
Leitão, Alexandre
Parkhouse, Robert Michael Evans
author_role author
author2 Moura, Pedro Luís
Ventura, Sónia
Leitão, Alexandre
Parkhouse, Robert Michael Evans
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Correia, Silvia
Moura, Pedro Luís
Ventura, Sónia
Leitão, Alexandre
Parkhouse, Robert Michael Evans
dc.subject.por.fl_str_mv African swine fever virus
I329L protein
Toll-like receptor
Immune evasion
Innate immunity
topic African swine fever virus
I329L protein
Toll-like receptor
Immune evasion
Innate immunity
description Research Areas: Virology
publishDate 2023
dc.date.none.fl_str_mv 2023-06-04T20:20:44Z
2023-02-05
2023-02-05T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.5/27882
url http://hdl.handle.net/10400.5/27882
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Correia S, Moura PL, Ventura S, Leitão A, Parkhouse RME. 2023. I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV). Viruses,15(2):445. DOI: https://doi.org/10.3390/v15020445
10.3390/v15020445
1999-4915
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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