Background Maedi/Visna virus (MVV) is a contagious viral pathogen that causes considerable economic losses to the sheep industry worldwide. Objectives In China, MVV has been detected in several regions, but its molecular characteristics and genetic variations were not thoroughly investigated. Methods Therefore, in this study, we conducted next-generation sequencing on an MVV strain obtained from northwest China to reveal its genetic evolution via phylogenetic analysis. Results A MVV strain obtained from Inner Mongolia (NM) of China was identified. Sequence analysis indicated that its whole-genome length is 9193 bp. Homology comparison of nucleotides between the NM strain and reference strains showed that the sequence homology of gag and env were 77.1%–86.8% and 67.7%–75.5%, respectively. Phylogenetic analysis revealed that the NM strain was closely related to the reference strains isolated from America, which belong to the A2 type. Notably, there were 5 amino acid insertions in variable region 4 and a highly variable motif at the C-terminal of the surface glycoprotein (SU5). Conclusions The present study is the first to show the whole-genome sequence of an MVV obtained from China. The detailed analyses provide essential information for understanding the genetic characteristics of MVV, and the results enrich the MVV library.

Background Ovine pulmonary adenomatosis (OPA) is a contagious lung epithelial tumor of sheep caused by jaagsiekte sheep retrovirus (JSRV), which causes severe economic losses for the sheep industry in the world. The specific oncogenic mechanism of JSRV is not yet clarified. Methods In this study, RNA was extracted from lung tissues of 3 naturally infected OPA cases and 3 healthy individuals for transcriptome sequencing (RNA-Seq). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the sequencing data. Immunohistochemistry (IHC) and western blot (WB) were performed to confirm the signaling pathway enriched by DEGs that was activated in naturally infected OPA cases. Cell viability, wound-healing, transwell and colony formation assays were performed to assess the cell malignant transformation of sheep trophoblast cells (STCs) transformed with JSRV- env lentivirus in vitro, and then WB was performed to confirm the signaling pathway that had been validated in the lung tissues. Results A total of 366 DEGs (154 up-regulated and 212 down-regulated) were identified by RNA-Seq of lung tissues of naturally infected OPA cases and healthy individuals. GO analysis showed that 366 DEGs were significantly enriched in 178 GO terms, including 114 biological processes, 19 cellular components and 45 molecular functions. KEGG analysis showed that the DEGs mainly enriched in cell proliferation, differentiation, apoptosis and migration, such as PI3K/Akt/mTOR, MAPK and Hippo signaling pathway, and Hippo signaling pathway has never been reported in naturally infected OPA cases. qRT-PCR results of 10 DEGs which were selected randomly were consistent with RNA-Seq results. The protein expression of Hippo signaling pathway were up-regulated in naturally infected OPA lung tissues. Cell viability, wound-healing, transwell and colony formation assays confirmed that JSRV- env lentivirus caused malignant transformation of STCs and JSRV Env increased the protein expression of Hippo signaling pathway. Conclusions This research first identified the changes in the transcriptome level of naturally infected OPA lung tissues. These data confirm that the Hippo signaling pathway is involved in the mechanism of OPA, clarify the interaction between Hippo signaling pathway and JSRV Env, provide further evidence for the tumorigenic mechanism of JSRV.

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.