Epigenetic Factor MicroRNAs Likely Mediate Vaccine Protection Efficacy against Lymphomas in Response to Tumor Virus Infection in Chickens through Target Gene Involved Signaling Pathways.

Simple Summary: Epigenetic factor microRNAs may modulate vaccine protective efficacy well, supported by experimental data showing that the expression of some microRNAs drastically differs between well-protected and poorly protected genetic lines of chickens. Marek's disease vaccination and virus challenge trials were conducted in two genetically divergent inbred lines of chickens, and hundreds of microRNAs were identified. However, a small number of miRNAs were observed with significant differential expression per line per vaccination treatment group. One of the vaccines was HVT, which reportedly protects the two lines of birds with a significant difference. The target genes of the differentially expressed miRNAs in response to HVT were reportedly involved with many Gene Ontology terms and pathways, which suggests there is a high complexity of the genetic/epigenetic mechanism modulating vaccine protective efficacy. 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-β, 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. [ABSTRACT FROM AUTHOR]