Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2022
Publication Date: 7/19/2022
Citation: Ma, H., Lippolis, J.D., Casas, E. 2022. Expression profiles and interaction of microRNA and transcripts in response to bovine leukemia virus exposure. Frontiers in Veterinary Science. 9. Article 887560. https://doi.org/10.3389/fvets.2022.887560.
Interpretive Summary: Bovine Leukemia Virus (BLV) produces leukosis, which can lead to leukemia in cattle, producing losses to the cattle industry due to loss of milk production and condemnation of carcasses. Small pieces of RNA, called microRNAs that circulate in cattle, are known to regulate gene expression. RNA is produced by transcribing DNA. The RNA is called a transcript. The goal of this study was to establish if there were differences in expression of microRNAs and transcripts, between cattle with and without exposure to BLV. An additional goal was to establish the association between microRNAs and transcripts to understand the role microRNAs play in the expression of transcripts when cattle is exposed to BLV. Five microRNAs were identified as having differences in expression, as well as sixty-four differentially expressed transcripts between both groups of cattle. The five microRNAs targeted seventeen of the sixty-four transcripts. When using prediction criteria, it was established that targets of the microRNAs were related to biosynthetic processes, which could be associated with replication of the virus. This indicates that the microRNAs fine-tune most of the target transcripts responding to BLV exposure. Further studies are required to establish the role these microRNAs, transcripts, and their interactions play in the molecular mechanisms of BLV infection, to uncover possible ways to prevent the infection or the development of the condition.
Technical Abstract: Bovine leukemia virus (BLV) infection in cattle is omnipresent, which causes significantly economical losses worldwide. The objective of this study was to determine microRNA (miRNA) and transcript profiles, and to establish their relationship in response to exposure to the virus. Small non-coding and messenger RNA were extracted and sequenced from serum and white blood cells (WBC) derived from seven BLV seropositive and seven seronegative cows. Transcriptomic profiles were generated by sequencing RNA libraries from WBC. Bta-miR-206 and bta-miR-133a-3p were differentially expressed in serum (P < 0.05). In WBC, bta-miR-335-3p, bta-miR-375, and bta-novel-miR76-3p were differentially expressed (P < 0.03). There were 64 differentially expressed transcripts (DETs). Gene ontology (GO) analysis of the DETs overexpressed in the seropositive group which were response to stimulus and immune system process, showed that the DETs negative regulated viral life cycle and viral entry or release from host cells. The DETs depleted in the seropositive group revealed down-regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I. The differentially expressed miRNAs targeted 17 DETs, among which the expressions of bta-miR-133a-3p and bta-miR-335-3p were significantly negative correlated with the expressions of ENSBTAT00000079143 and ENSBTAT00000066733 respectively. Under high prediction criteria, 90 targets of the differentially expressed miRNAs were all non-DETs. The most enriched biological process GOs of the targets was the RNA-dependent DNA biosynthetic process, which could be associated with virus replication. These results indicated that the differentially expressed miRNAs fine-tune most of the target genes in responding to BLV exposure. In addition, Bta-miR-206 interacted with BLV regulatory genes rex and tax by targeting their coding regions. A further study of the miRNAs and the genes may reveal the molecular mechanisms of BLV infection and uncover possible ways to prevent the infection.