Unveiling the functional landscape of A-to-I RNA editing associated with Marek’s disease in chickens
4 affiliations
- 1Department of Animal and Avian Science, University of Maryland, College Park, Maryland, United States of America
- 2Allen Institute for Brain Science, Seattle, Washington, United States of America
- 3U.S. Department of Agriculture, Agricultural Research Service, U.S. National Poultry Research Center, Athens, Georgia, United States of America
- 4Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, United States of America
Abstract
Genetic improvement of disease resistance against viral infections represents a longstanding and formidable challenge in animal breeding. The antiviral innate immune response is highly regulated at the RNA level, especially through RNA modifications. Adenosine-to-Inosine (A-to-I) RNA editing modifies the mRNA sequence. Growing evidence shows that this type of RNA editing plays a key role in mediating cellular responses to viral infections and disease resistance. However, the role of RNA editing in cellular response to MD remains unclear. In this study, we examined A-to-I editing in CD4+ T cells during Marek’s disease virus (MDV) infection. By comparing MD-resistant and susceptible chicken lines, we identified 642 A-to-I RNA editing events in CD4+ T cells, most of which were located within repeat elements, particularly in the CR1 family. We observed differences in RNA editing levels and counts between the two chicken lines with different infection statuses, indicating distinct editing patterns across genetic backgrounds and infection states. Additionally, ADAR (adenosine deaminases acting on RNA) expression was correlated with RNA editing frequency. We identified 21 RNA editing sites (RESs) associated with gene expression and 42, 14, and 38 RESs with predicted effects on amino acid sequences, alternative splicing, and miRNA-target binding, respectively. A comparative analysis revealed 131 group-specific RESs and 21 RESs shared across groups. Functional enrichment analysis of genes associated with group-specific RESs highlighted several terms related to MD resistance, including the MHC class I protein complex in non-infected MD-resistant birds. Significantly, we identified two L63-specific candidate RNA editing sites, chr6:26,600,122 in MXI1 and chr16:1,716,632 in MHCY57, which were predicted to affect gga-miR-1759-3p binding and amino acid sequence, respectively. Our findings reveal the landscape of A-to-I RNA editing in CD4 ⁺ T cells during MDV infection and provide new insights into its potential association with immune regulation and MD resistance. Author summary: Marek’s disease (MD) is a contagious viral disease of chickens that causes immune suppression, tumors, and economic losses to the poultry industry. Lines 63 and 72 are well-established chicken models for MD resistance and susceptibility, respectively, but the molecular basis of this difference remains unclear. We investigated whether RNA editing, a process that changes RNA after it is produced, is associated with differences in host responses between MD-resistant and MD-susceptible chickens. By examining splenic CD4⁺ T cells from MDV-infected and uninfected chickens of the resistant and susceptible lines, we identified hundreds of RNA editing events. These events were associated with differences in gene expression or were predicted to affect protein sequences, RNA processing, and interactions with small regulatory RNAs. We also identified two editing events in resistant chickens that may influence genes involved in immune regulation and tumor control. Our study highlights candidate RNA editing events associated with differential host responses to MDV infection. These findings improve our understanding of disease resistance and may inform future disease-resistant breeding and control strategies.
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BibTeX
@article{niu2026unveiling,
title = {{Unveiling the functional landscape of A-to-I RNA editing associated with Marek’s disease in chickens}},
author = {Qunhao Niu and Yi Ding and Longbin Yang and John R. Dunn and Huanmin Zhang and Keji Zhao and Jiuzhou Song},
journal = {PLOS Pathogens},
year = {2026},
month = nov,
doi = {10.1371/journal.ppat.1014743},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014743},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unveiling the functional landscape of A-to-I RNA editing associated with Marek’s disease in chickens
AU - Qunhao Niu
AU - Yi Ding
AU - Longbin Yang
AU - John R. Dunn
AU - Huanmin Zhang
AU - Keji Zhao
AU - Jiuzhou Song
PY - 2026
DA - 2026/11/05
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014743
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014743
AB - Genetic improvement of disease resistance against viral infections represents a longstanding and formidable challenge in animal breeding. The antiviral innate immune response is highly regulated at the RNA level, especially through RNA modifications. Adenosine-to-Inosine (A-to-I) RNA editing modifies the mRNA sequence. Growing evidence shows that this type of RNA editing plays a key role in mediating cellular responses to viral infections and disease resistance. However, the role of RNA editing in cellular response to MD remains unclear. In this study, we examined A-to-I editing in CD4+ T cells during Marek’s disease virus (MDV) infection. By comparing MD-resistant and susceptible chicken lines, we identified 642 A-to-I RNA editing events in CD4+ T cells, most of which were located within repeat elements, particularly in the CR1 family. We observed differences in RNA editing levels and counts between the two chicken lines with different infection statuses, indicating distinct editing patterns across genetic backgrounds and infection states. Additionally, ADAR (adenosine deaminases acting on RNA) expression was correlated with RNA editing frequency. We identified 21 RNA editing sites (RESs) associated with gene expression and 42, 14, and 38 RESs with predicted effects on amino acid sequences, alternative splicing, and miRNA-target binding, respectively. A comparative analysis revealed 131 group-specific RESs and 21 RESs shared across groups. Functional enrichment analysis of genes associated with group-specific RESs highlighted several terms related to MD resistance, including the MHC class I protein complex in non-infected MD-resistant birds. Significantly, we identified two L63-specific candidate RNA editing sites, chr6:26,600,122 in MXI1 and chr16:1,716,632 in MHCY57, which were predicted to affect gga-miR-1759-3p binding and amino acid sequence, respectively. Our findings reveal the landscape of A-to-I RNA editing in CD4 ⁺ T cells during MDV infection and provide new insights into its potential association with immune regulation and MD resistance. Author summary: Marek’s disease (MD) is a contagious viral disease of chickens that causes immune suppression, tumors, and economic losses to the poultry industry. Lines 63 and 72 are well-established chicken models for MD resistance and susceptibility, respectively, but the molecular basis of this difference remains unclear. We investigated whether RNA editing, a process that changes RNA after it is produced, is associated with differences in host responses between MD-resistant and MD-susceptible chickens. By examining splenic CD4⁺ T cells from MDV-infected and uninfected chickens of the resistant and susceptible lines, we identified hundreds of RNA editing events. These events were associated with differences in gene expression or were predicted to affect protein sequences, RNA processing, and interactions with small regulatory RNAs. We also identified two editing events in resistant chickens that may influence genes involved in immune regulation and tumor control. Our study highlights candidate RNA editing events associated with differential host responses to MDV infection. These findings improve our understanding of disease resistance and may inform future disease-resistant breeding and control strategies.
SN - 1553-7374
ER -