ArticlePLoS pathogens2024
The I7L protein of African swine fever virus is involved in viral pathogenicity by antagonizing the IFN-γ-triggered JAK-STAT signaling pathway through inhibiting the phosphorylation of STAT1.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Transcriptome analysis of African swine fever virus I9R-mediated modulation of host antiviral immunity.Virus research · 2026Article
- African swine fever virus pE199L, as a mitophagy receptor, suppresses antiviral innate immunity to promote viral replication.Autophagy · 2026Article
- Review
- African Swine Fever Virus pD345L Suppresses JAK-STAT Signaling by Selectively Triggering STAT1 Degradation.International journal of molecular sciences · 2026Article
- Resveratrol inhibits African swine fever virus replicationEmerging microbes & infections · 2025Article
- Immunoevasion strategies for African swine fever virus: Modulation of antigen presentation pathways.Virulence · 2025Review
- Rinderine suppresses African swine fever virus replication in porcine alveolar macrophages by dual targeting of membrane-associated profilin 1 and phosphatidylethanolamine.Emerging microbes & infections · 2025Article
- African swine fever virus MGF505-4R facilitates cGAS degradation through TOLLIP-mediated selective autophagy and inhibits the formation of ISGF3 to evade innate immunity.Veterinary research · 2025Article
- Advances in African swine fever virus molecular biology and host interactions contributing to new tools for control.Journal of virology · 2025Review
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Abstract
Cell-passage-adapted strains of African swine fever virus (ASFV) typically exhibit substantial genomic alterations and attenuated virulence in pigs. We have indicated that the human embryonic kidney (HEK293T) cells-adapted ASFV strain underwent genetic alterations and the I7L gene in the right variable region was deleted compared with the ASFV HLJ/2018 strain (ASFV-WT). A recent study has revealed that the deletion of the I7L-I11L genes results in attenuation of virulent ASFV in vivo, but the underlying mechanism remains largely unknown. Therefore, we hypothesized that the deletion of the I7L gene may be related to the pathogenicity of ASFV in pigs. We generated the I7L gene-deleted ASFV mutant (ASFV-ΔI7L) and found that the I7L gene deletion does not influence the replication of ASFV in primary porcine alveolar macrophages (PAMs). Using transcriptome sequencing analysis, we identified that the differentially expressed genes in the PAMs infected with ASFV-ΔI7L were mainly involved in antiviral immune responses induced by interferon gamma (IFN-γ) compared with those in the ASFV-WT-infected PAMs. Meanwhile, we further confirmed that the I7L protein (pI7L) suppressed the IFN-γ-triggered JAK-STAT signaling pathway. Mechanistically, pI7L interacts with STAT1 and inhibits its phosphorylation and homodimerization, which depends on the tyrosine at position 98 (Y98) of pI7L, thereby preventing the nuclear translocation of STAT1 and leading to the decreased production of IFN-γ-stimulated genes. Importantly, ASFV-ΔI7L exhibited reduced replication and virulence compared with ASFV-WT in pigs, likely due to the increased production of IFN-γ-stimulated genes, indicating that pI7L is involved in the virulence of ASFV. Taken together, our findings demonstrate that pI7L is associated with pathogenicity and antagonizes the IFN-γ-triggered JAK-STAT signaling pathway via inhibiting the phosphorylation and homodimerization of STAT1 depending on the Y98 residue of pI7L and the Src homology 2 domain of STAT1, which provides more information for understanding the immunoevasion strategies and designing the live attenuated vaccines against ASFV infection.
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