Lumpy skin disease virus 001/156 protein is a virulence factor that suppresses interferon production through impairing IRF3 dimerization.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Virulence Factors*/genetics ; Virulence Factors*/metabolism ; Interferon Regulatory Factor-3*/metabolism ; Interferon Regulatory Factor-3*/genetics ; Viral Proteins*/metabolism ; Viral Proteins*/genetics ; Lumpy skin disease virus*/pathogenicity ; Lumpy skin disease virus*/genetics ; Lumpy skin disease virus*/metabolism ; Lumpy skin disease virus*/immunology ; Interferons*/biosynthesis ; Interferons*/metabolism ; Lumpy Skin Disease*/virology ; Lumpy Skin Disease*/metabolism ; Lumpy Skin Disease*/immunology; Animals ; Cattle ; Virus Replication ; Humans ; Protein Multimerization

Competing Interests: The authors have declared that no competing interests exist.
Lumpy skin disease virus (LSDV), a member of the genus Capripoxvirus within the family Poxviridae, causes significant disease in cattle and is classified as a notifiable disease by the World Organization for Animal Health (WOAH). The virus contains a double-stranded linear DNA genome of approximately 151 kbp, encoding 156 predicted open reading frames (ORFs) for various proteins. However, only a limited number of these proteins have been characterized, with the functions of many-particularly those encoded within the inverted terminal repeat (ITR) regions-remaining largely unknown. In this study, we utilized homologous recombination to generate LSDV mutants with deletions of the LSDV 001/156 gene to investigate its role. LSDV 001/156, an uncharacterized protein located within the ITR region, was identified as a late-expressed gene product incorporated into virions and involved in viral replication. Further analysis revealed that LSDV 001/156 acts as a negative regulator of the interferon (IFN) signaling pathway. It interacts with interferon regulatory factor 3 (IRF3), disrupting its dimerization and nuclear translocation, thereby attenuating IFN production. Functional studies demonstrated that the LSDV mutant lacking the 001/156 gene exhibited reduced replication and virulence in cattle compared to the wild-type virus, likely due to enhanced IFN responses in the absence of this immune-evasive protein. In summary, our findings uncover a novel role of the LSDV 001/156 gene in modulating the host intrinsic antiviral response, shedding light on the mechanisms underlying LSDV pathogenesis. This study highlights the importance of ITR-encoded genes in immune evasion and virulence, providing new insights into LSDV biology and its interactions with the host immune system.
(Copyright: © 2025 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Virulence Factors)
0 (Interferon Regulatory Factor-3)
0 (Viral Proteins)
9008-11-1 (Interferons)

Date Created: 20250723 Date Completed: 20250731 Latest Revision: 20250802

20250802

PMC12313062

10.1371/journal.ppat.1013362

40700455