Dysregulation of immune gene expression profiles during HTLV-1 infection

Abstract

BackgroundHuman T-lymphotropic virus type 1 (HTLV-1) is the main cause of adult T cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of this study was to evaluate the dysregulation of immune genes that may be involved in the pathogenesis of ATLL using microarray datasets. MethodThe gene expression profiles of ATLL cases (GSE19080) were obtained from GEO database. Next, the quality and reliability of data were evaluated by MetaQC, and the expression data in each group were normalized by affy package. Subsequently, the R package MetaDE was applied for the analysis of differentially expressed genes (DEGs). Using STRING database, protein-protein interaction network (PPIN) was constructed for hub DEGs. Finally, online servers including STRING, Enrichr, and KEGG pathway were applied for gene enrichment and interpretation of the results. Results65 significant hub DEGs were divided in three groups, normal health, asymptomatic carrier and ATLL patients. The PPIN analysis between hub DEGs was carried out by STRING. Enrichment analysis revealed that the hub DEGs were involved in various pathways such as apoptosis, proliferation of T cell, Ras signaling, MAPK signaling, NF-κB signaling, integrin signaling, P53 signaling, angiogenesis, tissue invasion, and DNA damage process. ConclusionAccording to the present study, HTLV-1 appears to cause inflammation by enhancing cell proliferation. During the HTLV-1 infection, dysregulation of immune genes such as IL-10, TGF-β, JAK, BCL2, etc. result in immortalization of HTLV-1-infected CD4+ T cells, and eventually progression to ATLL.