Epigenetic factor microRNAs likely mediate vaccine protection efficacy against lymphomas in response to tumor virus infection in chickens through target gene involved signaling pathways

Authors: ZHANG, LEI - Chinese Academy Of Agricultural Sciences; XIE, QINGMEI - South China Agricultural Univerisity; CHANG, SHUANG - Shandong Agricultural University; AI, YONGXING - Jilin University; DONG, KUNZHE - Augusta University; Zhang, Huanmin

Submitted to: Veterinary Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2024
Publication Date: 3/22/2024
Citation: Zhang, L., Xie, Q., Chang, S., Ai, Y., Dong, K., Zhang, H. 2024. Epigenetic factor microRNAs likely mediate vaccine protection efficacy against lymphomas in response to tumor virus infection in chickens through target gene involved signaling pathways. Veterinary Sciences. 11(4):139. https://doi.org/10.3390/vetsci11040139.
DOI: https://doi.org/10.3390/vetsci11040139

Interpretive Summary: Marek’s disease (MD) is a serious threat to the poultry industry characterized by tumors in susceptible birds that are induced by Marek’s disease virus (MDV), the causative pathogen. Currently, MD is controlled in commercial flocks through widespread vaccination. However, the repeated emergence of more virulent MDV field strains requires continued studies to identify improved and more effective control measures. To gain insights on the underlying biology of the disease, we found a number of microRNAs, a type of short RNA molecule that influences the expression of genes, that correlated with MD genetic resistance or response to MD vaccines. This finding should lead to the selective breeding of chickens that are more genetically resistant to MD or respond more favorably to MD vaccines. If true, then both the industry and consumer would benefit from reduced disease incidence and healthier chickens.

Technical Abstract: Epigenetic factors, including microRNAs (miRNAs), play an important role in affecting gene expression and, therefore, are involved in various biological processes including immunity protection against tumors. Marek’s disease (MD) is a highly contagious disease of chickens caused by the MD virus (MDV). MD has been primarily controlled by vaccinations. MD vaccine efficacy might, in part, be dependent on modulations of a complex set of factors including host epigenetic factors. This study was designed to identify differentially expressed miRNAs in the primary lymphoid organ, bursae of Fabricius, in response to MD vaccination followed by MDV challenge in two genetically divergent inbred lines of White Leghorns. Small RNA sequencing and bioinformatic analyses of the small RNA sequence reads identified hundreds of miRNAs among all the treatment groups. A small portion of the identified miRNAs was differentially expressed within each of the four treatment groups, which were HVT or CVI988/Rispens vaccinated line 63-resistant birds and line 72-susceptible birds. A direct comparison between the resistant line 63 and susceptible line 72 groups vaccinated with HVT followed by MDV challenge identified five differentially expressed miRNAs. Gene Ontology analysis of the target genes of those five miRNAs revealed that those target genes, in addition to various GO terms, are involved in multiple signaling pathways including MAPK, TGF-ß, ErbB, and EGFR1 signaling pathways. The general functions of those pathways reportedly play important roles in oncogenesis, anti-cancer immunity, cancer cell migration, and metastatic progression. Therefore, it is highly likely that those miRNAs may, in part, influence vaccine protection through the pathways.