Ma Hao, Lippolis John D, Casas Eduardo
Ruminant Disease and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, United States.
Front Vet Sci. 2022 Jul 19;9:887560. doi: 10.3389/fvets.2022.887560. eCollection 2022.
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 noncoding and messenger RNA were extracted and sequenced from serum and white blood cells (WBCs) 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 ( < 0.05). In WBC, bta-miR-335-3p, bta-miR-375, and bta-novel-miR76-3p were differentially expressed ( < 0.03). There were 64 differentially expressed transcripts (DETs). Gene ontology (GO) analysis of the DETs overexpressed in the seropositive group with GOs of response to stimulus and immune system process predicted that the DETs could potentially negatively regulate viral life cycle and viral entry or release from host cells. In addition, the DETs depleted in the seropositive group could play a role in the downregulation of antigen processing and presentation of endogenous peptide antigen 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 negatively 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 GO term of the targets was the RNA-dependent DNA biosynthetic process, which could be associated with virus replication. These results suggested 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 and 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.
牛白血病病毒（BLV）在牛群中的感染无处不在，在全球范围内造成了巨大的经济损失。本研究的目的是确定微小RNA（miRNA）和转录组谱，并建立它们在病毒暴露反应中的关系。从7头BLV血清阳性和7头血清阴性奶牛的血清和白细胞（WBC）中提取小非编码RNA和信使RNA并进行测序。通过对WBC的RNA文库进行测序生成转录组谱。Bta-miR-206和bta-miR-133a-3p在血清中差异表达（<0.05）。在WBC中，bta-miR-335-3p、bta-miR-375和bta-新-miR76-3p差异表达（<0.03）。有64个差异表达转录本（DET）。对血清阳性组中过表达的DET进行基因本体（GO）分析，其与刺激反应和免疫系统过程的GO预测这些DET可能对病毒生命周期以及病毒进入或从宿主细胞释放具有潜在的负调控作用。此外，血清阳性组中减少的DET可能在内源性肽抗原MHC I类的抗原加工和呈递下调中发挥作用。差异表达的miRNA靶向17个DET，其中bta-miR-133a-3p和bta-miR-335-3p的表达分别与ENSBTAT00000079143和ENSBTAT00000066733的表达显著负相关。在高预测标准下，差异表达miRNA的90个靶标均为非DET。靶标的最富集生物过程GO术语是RNA依赖性DNA生物合成过程，这可能与病毒复制有关。这些结果表明，差异表达的miRNA在对BLV暴露的反应中对大多数靶基因进行微调。此外，Bta-miR-206通过靶向其编码区与BLV调控基因和相互作用。对miRNA和基因的进一步研究可能揭示BLV感染的分子机制，并发现预防感染的可能方法。
