An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; Evidence from high-throughput data integration and meta-analysis

Mozhgani, S. H. and Piran, M. and Zarei-Ghobadi, M. and Jafari, M. and Jazayeri, S. M. and Mokhtari-Azad, T. and Teymoori-Rad, M. and Valizadeh, N. and Farajifard, H. and Mirzaie, M. and Khamseh, A. and Rafatpanah, H. and Rezaee, S. A. and Norouzi, M. (2019) An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; Evidence from high-throughput data integration and meta-analysis. Retrovirology, 16 (1).

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Background: Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results: High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions: High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases. © 2019 The Author(s).

Item Type: Article
Additional Information: Export Date: 16 February 2020 Correspondence Address: Rezaee, S.-A.; Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical SciencesIran; email:
Uncontrolled Keywords: HAM/TSP High-throughput data integration HTLV-1 HTLV-1-associated myelopathy/tropical spastic paraparesis Meta-analysis Microarray carrier proteins and binding proteins cytokine ELAV like protein 2 interferon messenger RNA STAT1 protein string protein transporter associated with antigen processing 1 unclassified drug virus RNA Article asymptomatic carrier cell cycle comparative study cytotoxic T lymphocyte disease association down regulation flow cytometry gene expression regulation gene identification gene regulatory network genetic association helper cell high throughput sequencing HTLV-1 infection hub gene human Human T-lymphotropic virus 1 immune response JAK-STAT signaling meta analysis (topic) nonhuman pathogenesis protein protein interaction PSMB8 gene real time polymerase chain reaction RNA translation spinal cord disease STAT1 gene TAP1 gene tropical spastic paraparesis upregulation virus carrier virus gene
Subjects: QW Microbiology and Immunology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib1 lib1
Date Deposited: 21 Jun 2020 09:28
Last Modified: 21 Jun 2020 09:28

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