IDENTIFICATION OF TRANSCRIPTIONAL BIOMARKERS ASSOCIATED WITH HTLV-1 INFECTION MAIN CLINICAL MANIFESTATIONS
HTLV-1, Gene Expression, Meta-analysis, ATLL, HAM/TSP
Adult T-cell Lymphotropic Virus 1 (HTLV-1) is a sexually transmitted human retrovirus that exhibits preferential CD4+ T-cell tropism. Although most individuals infected with this virus remain asymptomatic (ASS), the main clinical manifestations such as HTLV-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and Adult T-Cell Leukemia/Lymphoma (ATLL) are troublesome conditions. HAM/TSP is an inflammatory manifestation of the central nervous system that may culminate in partial loss of lower limbs movements. ATLL is a type of non-Hodgkin's lymphoma that usually leads to death. This work aims to propose differential transcriptional profile, suggestive of the HTLV-1-associated pathologies, and to investigate the implications of deregulation on gene expression. A meta-analysis of ten publicly available microarray datasets was performed to identify differentially expressed genes (DEGs). Enriched KEGG pathways analysis was performed. Protein-protein interaction (PPI) networks, module extraction and gene hubs selection were implemented with STRING, MCODE and CytoHubba. A total of 907, 368 and 150 DEGs were identified for ATLL, HAM/TSP, and ASS respectively. The KEGG analysis identified "Cancer Pathways" and "Endocytosis" as ATLL-enriched pathways in the set of upregulated and downregulated DEGs respectively. No enriched pathways were identified for the full set of HAM/TSP and ASS DEGs. From the PPI networks generated by STRING, three modules were extracted for each clinical manifestation. Combining the results from MCODE and CytoHubba, five hub genes selected for each condition. Only ATLL presented differentially expressed micro-RNAs: hsa-mir-21, directly involved in the development of the disease and hsa-mir-6840, which is still poorly known. This study generated a database of candidate genetic markers and enriched pathways for the clinical status associated with HTLV-1 infection, facilitating the definition and understanding of prognostic therapeutic biomarkers.