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Updated: Jun 17, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
UEV1A attenuates MDA5-mediated antiviral immune response by reducing its ubiquitination and aggregation
Jiaxin Wang1, Rongyao Sun1, Ting Li1
1College of Life Science, Hunan Normal University, Changsha, 410081, China.
Abstract:
Ubiquitin-conjugating enzyme variant 1A (UEV1A) is an E2 ubiquitin-conjugating enzyme and participates in several physiological processes. However, its role in teleost antiviral innate immune response remains unknown. In this study, we identified and characterized a black carp UEV1A homolog (bcUEV1A) as a novel regulator of black carp MDA5 (bcMDA5)-mediated antiviral signaling. bcUEV1A is composed of 164 amino acids containing a conserved ubiquitin-conjugation enzyme catalytic (UBCc) domain spanning residues 31-163. Quantitative real-time PCR (qRT-PCR) analysis showed that bcUEV1A gene transcription was dynamically regulated in host cells and immune-related tissues following viral infection or immunostimulant treatment. Immunoblot analysis indicated that bcUEV1A migrated at approximately 20 kDa, whereas immunofluorescence analysis revealed that it was localized in the cytoplasm and cell nucleus. Co-immunoprecipitation (co-IP) assay and immunofluorescence assays demonstrated that bcUEV1A specifically interacted with bcMDA5, and that both proteins were co-localized in the cytoplasm. Functional analyses further showed that bcUEV1A suppressed bcMDA5-mediated IFN promoter activation and antiviral activity. Mechanistically, bcUEV1A negatively regulated bcMDA5-mediated antiviral immunity by reducing bcMDA5 polyubiquitination, oligomerization, and dimerization. Collectively, these findings identify bcUEV1A as a critical negative regulator of bcMDA5-mediated antiviral immunity and provide new insight into the molecular mechanisms controlling MDA5-dependent antiviral immunity in teleost fish.
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