I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , |
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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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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799131670909026304 |