African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation

Barrado-Gil, Lucia, del Puerto, Ana, Galindo, Inmaculada, Cuesta-Geijo, Miguel Angel, Garcia-Dorival, Isabel ORCID: 0000-0002-5654-5662, de Motes, Carlos Maluquer and Alonso, Covadonga (2021) African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation. VIRUSES-BASEL, 13 (6). 1160-.

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Official URL: http://dx.doi.org/10.3390/v13061160

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	innate immunity, TLR, NF-kappa B, AP-1, IFN, STING, African swine fever virus, ubiquitin, E2 enzyme, ubiquitin-conjugating enzyme, ASFV
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	07 Feb 2022 12:24
Last Modified:	17 Oct 2023 16:27
DOI:	10.3390/v13061160
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3148410