Sequence and transcriptional activity analysis of long terminal repeat of endogenous and exogenous Jaagsiekte sheep retrovirus

Background: Sheep are an ideal model for studying endogenous and exogenous retroviruses. The exogenous Jaagsiekte sheep retrovirus (exJSRV) is a pathogenic agent responsible for ovine pulmonary adenocarcinoma. In infected sheep, it coexists with various highly related endogenous Jaagsiekte sheep retroviruses (enJSRV). Jaagsiekte sheep retrovirus integrates into the sheep genome in a proviral form whose long terminal repeat (LTR) regulates the expression of viral genes using host transcriptional mechanisms. LTR plays an important regulatory role in transcription and cell tropism. Methods We cloned the LTR genes of enJSRV and exJSRV and analyzed the differences between the two sequences using bioinformatics. Furthermore, we detected the transcriptional activity of LTRs in different cell types using the dual-luciferase system. Results Phylogenetic tree analysis showed that the LTRs of enJSRV and exJSRV were divided into two branches, and there were differences in transcription factor binding sites, CpG islands, and putative quadruplex-forming sequences. The dual-luciferase reporter system showed that the transcriptional activity of exJSRV LTR was significantly higher than that of enJSRV LTR in lung epithelial cells ( P  < 0.01). Conclusions This study provides a comprehensive analysis of the sequence features of the LTR of enJSRV and exJSRV. These findings support the importance of the LTR in the respective tissue specificities of enJSRV and exJSRV.