Next Article in Journal
Genetic and Pathogenic Characterization of QX(GI-19)-Recombinant Infectious Bronchitis Viruses in South Korea
Next Article in Special Issue
African Swine Fever Virus as a Difficult Opponent in the Fight for a Vaccine—Current Data
Previous Article in Journal
Emerging Hepatotropic Viruses in Cats: A Brief Review
Previous Article in Special Issue
Thoughts on African Swine Fever Vaccines
Article

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

1
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Ctra. de la Coruña km 7.5, 28040 Madrid, Spain
2
Department of Microbial Sciences, School of Biosciences and Medicine, University of Surrey, Stag Hill, Guildford GU2 7XH, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Manuel Borca
Received: 14 May 2021 / Revised: 11 June 2021 / Accepted: 14 June 2021 / Published: 17 June 2021
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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. View Full-Text
Keywords: innate immunity; TLR; NF-κB; AP-1; IFN; STING; African swine fever virus; ubiquitin; E2 enzyme; ubiquitin-conjugating enzyme; ASFV innate immunity; TLR; NF-κB; AP-1; IFN; STING; African swine fever virus; ubiquitin; E2 enzyme; ubiquitin-conjugating enzyme; ASFV
Show Figures

Figure 1

MDPI and ACS Style

Barrado-Gil, L.; del Puerto, A.; Galindo, I.; Cuesta-Geijo, M.Á.; García-Dorival, I.; de Motes, C.M.; Alonso, C. African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation. Viruses 2021, 13, 1160. https://0-doi-org.brum.beds.ac.uk/10.3390/v13061160

AMA Style

Barrado-Gil L, del Puerto A, Galindo I, Cuesta-Geijo MÁ, García-Dorival I, de Motes CM, Alonso C. African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation. Viruses. 2021; 13(6):1160. https://0-doi-org.brum.beds.ac.uk/10.3390/v13061160

Chicago/Turabian Style

Barrado-Gil, Lucía, Ana del Puerto, Inmaculada Galindo, Miguel Á. Cuesta-Geijo, Isabel García-Dorival, Carlos M. de Motes, and Covadonga Alonso. 2021. "African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation" Viruses 13, no. 6: 1160. https://0-doi-org.brum.beds.ac.uk/10.3390/v13061160

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop