The TGFβ Signaling Pathway Could Be Effective in the Pathogenesis of Human Lymphotropic Virus Type 1 Evidence from a Systems Biology Study

Background: Human T-cell lymphotropic virus type 1 (HTLV-1) is responsible for two critical human diseases: Adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most cases of HTLV-1 infection are asymptomatic and the prevalence of serious diseases like HAM/TSP and ATLL is not remarkable, their prognosis is poor. It has been assumed that various immunological responses, different interactions between the patient’s body and the virus, and clearly the virus itself, are responsible for pathogenesis. To prevent and manage the consequences of this oncogenic virus, we should clearly understand the molecular pathways and interactions between the HTLV-1 virus and human cells. Objectives: In this study, we aim to identify the most essential genes and microRNAs involved in the induction of ATLL disease and its laboratory confirmation. Methods: After a purposeful search in databases and a qualitative review of obtained data, the data were processed using R software, and miRNAs with different expressions (DEMs) were calculated according to the value of logFC. The gene targets of miRNAs were obtained using the miRDB online tool. The protein-protein interaction network of gene targets was drawn and analyzed with the STRING database. The sub-network was extracted using Cytoscape. Pathway analysis was conducted, and proteins participating in the enriched pathways were selected to propose the implicated signaling network using the information available on the website ENRICHR and KEGG message transduction. An intracellular control gene, RPLP0, and three other key genes were selected and evaluated in 10 healthy participants, 10 asymptomatic carriers (ACs), and 10 ATLL patients using real-time PCR. Results: Mir-20a-5p was identified as an essential microRNA with different expression in the patient group compared to the healthy and ACs. Transforming growth factor-beta 1 (TGF-β1), TGFBR1, and TGFBR2, which have a crucial role in disease pathogenesis, were identified. Conclusions: The results demonstrated that TGFBR1’s expression level was remarkably increased in ATLL patients compared to healthy donors and ACs. Further investigations are required to assess the prognostic and therapeutic function of these elements.