Gene Expression Profiling Reveals New Pathways and Genes Associated with Visna/Maedi Viral Disease

SIMPLE SUMMARY: Visna/Maedi is a disease caused by a small ruminant lentivirus (SRLV), with different symptoms in adult sheep such as pneumonia, arthritis, encephalitis and mastitis. SRLV infection in sheep is widespread across the world, with Europe showing the highest individual prevalence. There is currently no effective treatment for SRLV infections and, due to their constant changes, effective vaccine development has been and is still challenging. The dynamics of the sheep immune response to these virus infections is unclear, and changes in gene expression can help to explain the processes occurring in infected sheep. In this study, a gene expression microarray was used to identify the differentially expressed genes in infected and diseased sheep by comparing animals with different serologic statuses and with the presence of VM-characteristic clinical lesions in the lungs. The expression profile analysis revealed many interesting genes that may be associated with the viral infection process (such as OXT and a number of genes implicated in the Toll Like Receptors signaling network and complement pathway). This work improves our understanding of the sheep immune response against SRLVs. ABSTRACT: Visna/Maedi virus (VMV) is a lentivirus that infects the cells of the monocyte/macrophage lineage in sheep, goats and wild ruminants. Infection with VMV causes a multisystemic inflammatory disorder, which includes pneumonia, encephalitis, mastitis or arthritis. The immune response to VMV infection is complex, and the infection and pathogenesis of this virus are not totally characterized yet. In this work, a gene expression microarray was used to identify the differentially expressed genes in VMV infection and disease development by comparing sheep with different serologic status and with presence of VM-characteristic clinical lesions. The expression profile analysis has revealed many interesting genes that may be associated with the viral infection process. Among them, the OXT gene appeared significantly up-regulated, so the oxytocin-secreting system could play an essential role in VM disease. Moreover, some of the most significantly enriched functions in up-regulated genes appeared the complement pathway, which (in combination with the Toll-like receptor signaling network) could compose a mechanism in the VMV pathogenesis. Identifying the host genetic factors associated with VMV infection can be applied to develop strategies for preventing infection and develop effective vaccines that lead to therapeutic treatments.