Herpesvirus infection triggers excessive inflammation, contributing to tissue injury and disease severity, but the underlying drivers remain unclear. Here we identify EphA2 as a critical mediator of pseudorabies virus (PRV)-induced inflammatory response. Genetic or pharmacological inhibition of EphA2 reduced TNF-α production in PRV-infected cells and mice, alleviated liver and lung damage, and improved mice survival. Mechanistically, PRV infection promoted EphA2 phosphorylation at Ser-897, which activated NF-κB and MAPK pathways to drive TNF-α production. The PRV tegument protein UL40 directly bound the EphA2 kinase domain (residues 697–901), a region that also interacts with Akt. Unexpectedly, Akt acted as a negative regulator of inflammation, as its knockdown exacerbated cytokine production. UL40 competitively disrupted the constitutive EphA2–Akt complex in a time-dependent manner, relieving Akt-mediated restraint on EphA2 S897 phosphorylation. Accordingly, a UL40-deficient PRV mutant failed to enhance S897 phosphorylation, elicited lower inflammatory responses, and showed attenuated virulence in mice. Collectively, our findings reveal a proviral strategy whereby PRV UL40 hijacks EphA2 to counteract an intrinsic Akt-dependent inhibitory pathway. This UL40–EphA2–Akt cascade is a critical determinant of virus-induced inflammation, and EphA2 S897 represents a potential therapeutic target for mitigating alphaherpesvirus immunopathology.
Yutong Tian, Hang Yin, Jia-Xiang Fu et al.· Veterinary Research· 0 citations
Lactic acid bacteria (LAB) are regarded as promising probiotics with multiple beneficial properties for humans’ and animals’ health. In this study, ten LAB isolates were screened and Lactiplantibacillus plantarum (L. plantarum) CLPX21 was selected as a candidate strain with its probiotic potential based on in vitro screening of antimicrobial activity and environmental stress tolerance, including its resistance to acidic environments and bile salts. This strain displayed adhesion capacity with an auto-aggregation rate of 47.15% at 24 h, co-aggregation rates above 67% with pathogenic bacteria, and an ability to adhere to IPEC-J2 cells (6.37%). CLPX21 showed broad-spectrum antimicrobial activity against common foodborne pathogens including Escherichia coli (E. coli), Salmonella, and Staphylococcus aureus. In addition, CLPX21 inhibited E. coli biofilm formation. Furthermore, CLPX21 significantly suppressed E. coli-induced inflammatory cytokine production in mouse peritoneal macrophages. Importantly, CLPX21 did not exhibit hemolytic activity. Genomic analysis further revealed that the CLPX21 genome encoded multiple functional genes and gene clusters, including biosynthesis of bacteriocins and secondary metabolites associated with antimicrobial and antioxidant functions, which provide a genetic basis for its beneficial phenotypic characteristics. In conclusion, L. plantarum CLPX21 displays probiotic properties with potent antimicrobial and anti-inflammatory activities, representing a promising candidate strain for applications in the food and health industries.
Shichao Xu, Qian-Qian Fan, Hongdou Liu et al.· Microorganisms· 0 citations
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