MicroRNA profiling in the bursae of MDV-infected resistant and susceptible chicken lines

Authors: Heidari, Mohammad; ZHANG, LEI - Academy Of Agricultural Science; Zhang, Huanmin

Submitted to: Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/10/2020
Publication Date: 2/12/2020
Citation: Heidari, M., Zhang, L., Zhang, H. 2020. MicroRNA profiling in the bursae of MDV-infected resistant and susceptible chicken lines. Genomics. 112:2564-2571. https://doi.org/10.1016/j.ygeno.2020.02.009.
DOI: https://doi.org/10.1016/j.ygeno.2020.02.009

Interpretive Summary: Marek’s disease virus (MDV) is an alpha herpesvirus that induces depression, bursal/thymic atrophy, neurologic disorders, and rapid onset of T cell lymphomas in domestic chickens. MicroRNAs (miRNAs) a class of small, single stranded, noncoding RNAs that are transcribed from the genomes of all multicellular organisms and some viruses. MiRNAs govern post-transcriptional repression of their target genes by binding to the 3’ untranslated regions of mRNA. Virus-encoded miRNAs are implicated in pathogenicity, tumorigenesis, and host immune system evasion. Host and virus encoded miRNAs in MDV-induced tumorous tissues and transformed cell line have been investigated. However, the effect of MDV infection on host miRNA expression pattern in non-tumorous but atrophied lymphoid organs, such as bursa of Fabricius, has not been studied. Here, we performed comparative analysis of chicken microRNAs expression between the bursas of MD-resistant and susceptible chicken lines at 21 days post infection. Data obtained revealed significant differences in the expression pattern between control birds of both lines, infected and control of each line, and infected birds of both lines. Most of the differentially expressed miRNAs among the groups were unique miRNAs that have not been identified previously. Insertional mutation or deletion of miRNAs will provide insight into their molecular functions and may help in the development of recombinant vaccines against evolving more pathogenic strains.

Technical Abstract: Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by a cell-associated highly oncogenic avian alpha-herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, bursal/thymic atrophy, neurologic disorders, and rapid onset of T cell lymphomas. MicroRNAs (miRNAs) are small, noncoding RNAs transcribed from the genomes of all multicellular organisms and some viruses. MiRNAs play key roles in regulation of gene expression by base pairing with the 3’ untranslated regions of mRNA, thereby targeting translational suppression or mRNA degradation. Most of the virally encoded miRNAs belong to herpesviruses. MDV, a member of Herpesviridae, also encodes miRNAs that are associated with viral pathogenicity and oncogenesis. The effect of MDV infection on host miRNA expression pattern in non-tumorous but atrophied lymphoid organs, such as bursa of Fabricius, has not been studied. Here, we performed comparative analysis of chicken microRNAs expression between the bursae of MD-resistant (6-3) and susceptible (7-2) chicken lines at 21 days post infection. Fifteen differentially expressed (DE) miRNAs were detected when the control uninfected birds of line 6-3 were compared to the age-matched control birds of line 7-2. Eight of the DE microRNAs matched to previously identified chicken miRNAs. The remaining seven novel miRNAs mapped to chicken genome with no sequence homology to existing miRNAs in chicken miRbase. Comparison of bursa miRNAs from infected line 6-3 to control birds of the same line, identified 19 miRNAs with 18 being novel and only one matching a known miRNA. The smallest number of differentially expressed miRNAs were identified when bursae of infected birds of line 7-2 were compared to those of the age-matched control birds. Only eight novel and one previously known miRNA were identified. The largest number of DE miRNAs was identified when we compared the expression pattern of miRNAs between the infected birds of the resistant line 6-3 and susceptible line 7-2. Twenty-eight DE miRNAs were detected of which 25 were novel microRNAs that did not match any previously known chicken miRNAs and three microRNAs with homologous match to known miRNAs in chicken miRbase. Out of more than 300 novel miRNAs identified, 54 were DE between the chicken lines that might play a role in inducing resistance or susceptibility to MD.