Expression of Viral microRNAs in Serum and White Blood Cells of Cows Exposed to Bovine Leukemia Virus.

Bovine leukemia virus (BLV) affects the health and productivity of cattle. The virus causes abnormal immune function and immunosuppression. MicroRNAs (miRNAs) are involved in gene expression, having been associated with stress and immune response, tumor growth, and viral infection. The objective of this study was to determine the expression of circulating miRNAs produced by BLV in animals exposed to the virus. Sera from 14 animals were collected to establish IgG reactivity to BLV by ELISA, where seven animals were seropositive and seven were seronegative for BLV exposure. White blood cells (WBC) from each animal were also collected and miRNAs were identified by sequencing from sera and WBC. The seropositive group had higher counts of BLV miRNAs when compared to seronegative group in sera and WBC. Blv-miR-1-3p, blv-miR-B2-5p, blv-miR-B4-3p, and blv-miR-B5-5p were statistically significant ( < 0.00001) in serum with an average of 7 log2 fold difference between seropositive and seronegative groups. Blv-miR-B1-3p, blv-miR-B1-5p, blv-miR-B3, blv-miR-B4-3p, blv-miR-B4-5p, blv-miR-B5-5p were statistically significant ( < 1.08e) in WBC with an average of 7 log2 fold difference between the seropositive and the seronegative groups. Blv-miR-B2-3p and blv-miR-B2-5p were also statistically significant in WBC ( < 2.79e-17), with an average of 27 log2 fold difference between the seropositive and the seronegative groups. There were 18 genes identified as being potential targets for blv-miR-B1-5p, and 3 genes for blv-miR-B4-5p. Gene ontology analysis indicated that the target genes are mainly involved in the response to stress and in the immune system process. Several of the identified genes have been associated with leukemia development in humans and cattle. Differential expression of genes targeted by BLV miRNAs should be evaluated to determine their effect in BLV replication.