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Thymic single-cell RNA sequencing reveals the immunosuppressive microenvironment in chicken model simulating vertical transmission of recombinant ALV

Year: 2026

Type: article

Abstract: ABSTRACT Avian leukosis virus (ALV) induces immunosuppression and tumorigenesis. In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the transcriptional dynamics of thymic immune cells in specific-pathogen-free (SPF) chickens, which were intra-embryonic infected with the naturally recombinant ALV-FJ15TH0, at 1-day-old (d), 28d, and 56d post-hatch. Using subgroup-specific marker genes and cell state analysis, we identified six T-cell clusters, two B-cell clusters, and a macrophage cell cluster. Differential gene analysis revealed that ALV infection resulted in a significant enrichment of downregulated genes across all immune cell subsets at 28d. Functional enrichment analysis indicated that ALV infection activated the FoxO immunosuppressive pathway, PI3K pathway, MAPK pathway (CD4 + CD8 + T cells and M2 macrophages at 1d), multicellular synergistic regulation of the cancer pathway (CD4 + CD8 + T cells, M2 macrophages, and Cytotoxic T cells at 28d), and ErbB signaling pathway, Notch signaling pathway (CD4 + CD8 + T cells and M2 macrophages at 56d). Cell-cell communication analysis revealed that ALV infection induced the strongest predicted communication via the PPIA-BSG axis at 28 d. Analysis further inferred that CD147 (BSG) was associated with multiple signaling pathways, including MAPK/ERK and PI3K/AKT, which may contribute to the immunosuppressive microenvironment. BCL11B, SP3, and EP300 were identified as potential regulatory components with subset-specific associations with JUN, BRAF , and MYB , potentially involving the MAPK, PI3K/AKT, and FoxO signaling pathways. This study reveals the dynamic evolution of the thymic immune microenvironment following ALV-FJ15TH0 infection, providing a resource for understanding the molecular mechanisms underlying ALV-induced immunosuppression and offering a foundation for future investigation of its potential relationship with tumorigenesis.

Source: Poultry Science

DOI: 10.1016/j.psj.2026.108033