Upregulated host genes during the disease progression of bovine leukemia virus independent on overexpression of viral transcriptional regulators in vitro

Abstract

Abstract Bovine leukemia virus (BLV) is a member of the genus Deltaretrovirus within the Retroviridae family that infects bovine B cells, causing persistent lymphocytosis and enzootic bovine leukosis (EBL) in a small fraction of infected cattle. As changes in the profiles of the infected-cell transcriptome are important for BLV disease progression, comprehensive analyses to clarify gene expression in different disease states are required. In this study, we performed an RNA-seq analysis using samples from non-EBL cattle infected or uninfected with BLV. Subsequently, a transcriptome analysis was conducted in combination with previously obtained RNA-seq data from EBL cattle. We found several differentially expressed genes (DEGs) between the three groups; subsequently, after screening and validation of target DEGs using real-time reverse transcriptase polymerase chain reaction, we found that 12 target genes were significantly upregulated in EBL cattle compared to BLV-infected cattle without lymphoma. In addition, the expression levels of B4GALT6, ZBTB32, EPB4L1, RUNX1T1, HLTF, MKI67, and TOP2A were significantly and positively correlated with the proviral load in BLV-infected cattle. Overexpression experiments revealed that these changes were independent of BLV-tax or BLV-AS1-S expression in vitro. Our study provides additional information on host gene expression during BLV infection and EBL development, which may be helpful for understanding the complexity of transcriptome profiles during disease progression.