Omics & gene networks

Unveiling the Functional Landscape of RNA Editing Associated with Chicken Marek's Disease

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Abstract

Adenosine-to-Inosine (A-to-I) RNA editing, catalyzed by members of the ADAR family, results in modifications to the mRNA sequence. Accumulating evidence has demonstrated that this type of RNA editing plays a crucial role in mediating the cellular response to viral infections. Nevertheless, the role of RNA editing in the cellular response to Marek's disease (MD) remains unclear. Marek's disease virus (MDV) has undergone remarkable evolution toward more virulent strains and remains a persistent threat to the global poultry industry. MD-resistant Line 63 and MD-susceptible Line 72 are well-characterized chicken models that serve as valuable tools for investigating MD resistance. CD4+ T cells are the primary target of MDV, which infects and transforms them into cancerous lymphomas, resulting in multiple visceral tumors and immunosuppression in chickens. In this study, we investigated A-to-I RNA editing in CD4+ T cells during MDV infection between MD-resistant and susceptible chicken lines. Firstly, CD4⁺ T cells were isolated from chicken spleens by magnetic positive selection using PE-conjugated anti-chicken CD4 antibodies, yielding >90% purity as confirmed by flow cytometry. By integrating RNA-seq and whole-genome sequencing data, we applied REDItools to identify 647 A-to-I RNA editing events across 187 unique sites in CD4⁺ T cells. Notably, the majority of these events were located within genomic repetitive elements, with a significant enrichment in the CR1 family. The number of editing events differed significantly across lines and infection status, while editing levels showed relatively slight differences. Specifically, we observed that the more abundant A-to-I editing events occurred in the MD susceptible line. In contrast, the small number of editing events occurred in the resistant line, suggesting that immune regulatory mechanisms influenced by RNA editing differ across genetic backgrounds and infections. In coding genes, most editing events occur in the 3' UTR. Furthermore, we identified 21, 42, 14, and 38 RESs A-to-I editing events that contribute to gene expression, amino acid sequences, alternative splicing, and miRNA-target binding, respectively. Comparative analyses identified 131 group-specific RESs and 21 RESs shared among groups. Functional enrichment of group-specific RES-associated genes pinpointed several MD-resistance pathways (e.g., MHC class I protein complex in L63-control). More important, we pinpointed two functional Line 63-specific RESs including chr6:26,600,122 and chr16:1,716,632 may play important role in the resistance formation of Line 63. Collectively, our findings reveal the distinct landscape of A-to-I RNA editing in CD4+ T cells during MDV infection, providing novel insights into how RNA editing modulates MD resistance.

Keywords: 2026

How to Cite:

Niu, Q., Ding, Y., Yang, L., Dunn, J., Zhang, H. & Song, J., (2026) “Unveiling the Functional Landscape of RNA Editing Associated with Chicken Marek's Disease”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286551. doi: https://doi.org/10.31274/wcgalp.24047

Rights: 1