African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation
African swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune...
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MDPI AG
2021-06-01
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Online Access: | https://www.mdpi.com/1999-4915/13/6/1160 |
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author | Lucía Barrado-Gil Ana del Puerto Inmaculada Galindo Miguel Ángel Cuesta-Geijo Isabel García-Dorival Carlos Maluquer de Motes Covadonga Alonso |
author_facet | Lucía Barrado-Gil Ana del Puerto Inmaculada Galindo Miguel Ángel Cuesta-Geijo Isabel García-Dorival Carlos Maluquer de Motes Covadonga Alonso |
author_sort | Lucía Barrado-Gil |
collection | DOAJ |
description | African swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. Transient overexpression of UBCv1 impaired activation of NF-κB and AP-1 transcription factors induced by several agonists of these pathways. In contrast, activation of IRF3 and ISRE signaling upon stimulation with TRIFΔRIP, cGAS/STING or RIG-I-CARD remained unaltered. Experiments aimed at mapping UBCv1 inhibitory activity indicated that this viral protein acts upstream or at the level step of IKKβ. In agreement with this, UBCv1 was able to block p65 nuclear translocation upon cytokine stimulation, a key event in NF-ĸB signaling. Additionally, A549 stably transduced for UBCv1 showed a significant decrease in the levels of NF-ĸB dependent genes. Interestingly, despite the well-defined capacity of UBCv1 to conjugate ubiquitin chains, a mutant disabled for ubiquitylation activity retained similar immunomodulatory activity as the wild-type enzyme, suggesting that the two functions are segregated. Altogether these data suggest that ASFV UBCv1 manipulates the innate immune response targeting the NF-κB and AP-1 pathways and opens new questions about the multifunctionality of this enzyme. |
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issn | 1999-4915 |
language | English |
last_indexed | 2024-03-10T10:19:21Z |
publishDate | 2021-06-01 |
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series | Viruses |
spelling | doaj.art-3e2d3d29d37b4ceab70384ca0aa135ad2023-11-22T00:32:03ZengMDPI AGViruses1999-49152021-06-01136116010.3390/v13061160African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB ActivationLucía Barrado-Gil0Ana del Puerto1Inmaculada Galindo2Miguel Ángel Cuesta-Geijo3Isabel García-Dorival4Carlos Maluquer de Motes5Covadonga Alonso6Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, SpainDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, SpainDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, SpainDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, SpainDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, SpainDepartment of Microbial Sciences, School of Biosciences and Medicine, University of Surrey, Stag Hill, Guildford GU2 7XH, UKDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, SpainAfrican swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. Transient overexpression of UBCv1 impaired activation of NF-κB and AP-1 transcription factors induced by several agonists of these pathways. In contrast, activation of IRF3 and ISRE signaling upon stimulation with TRIFΔRIP, cGAS/STING or RIG-I-CARD remained unaltered. Experiments aimed at mapping UBCv1 inhibitory activity indicated that this viral protein acts upstream or at the level step of IKKβ. In agreement with this, UBCv1 was able to block p65 nuclear translocation upon cytokine stimulation, a key event in NF-ĸB signaling. Additionally, A549 stably transduced for UBCv1 showed a significant decrease in the levels of NF-ĸB dependent genes. Interestingly, despite the well-defined capacity of UBCv1 to conjugate ubiquitin chains, a mutant disabled for ubiquitylation activity retained similar immunomodulatory activity as the wild-type enzyme, suggesting that the two functions are segregated. Altogether these data suggest that ASFV UBCv1 manipulates the innate immune response targeting the NF-κB and AP-1 pathways and opens new questions about the multifunctionality of this enzyme.https://www.mdpi.com/1999-4915/13/6/1160innate immunityTLRNF-κBAP-1IFNSTING |
spellingShingle | Lucía Barrado-Gil Ana del Puerto Inmaculada Galindo Miguel Ángel Cuesta-Geijo Isabel García-Dorival Carlos Maluquer de Motes Covadonga Alonso African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation Viruses innate immunity TLR NF-κB AP-1 IFN STING |
title | African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation |
title_full | African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation |
title_fullStr | African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation |
title_full_unstemmed | African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation |
title_short | African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation |
title_sort | african swine fever virus ubiquitin conjugating enzyme is an immunomodulator targeting nf κb activation |
topic | innate immunity TLR NF-κB AP-1 IFN STING |
url | https://www.mdpi.com/1999-4915/13/6/1160 |
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