Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study
Abstract Background Human T-cell Leukemia Virus type-1 (HTLV-1) is a retrovirus that causes two diseases including Adult T-cell Leukemia/Lymphoma (ATLL cancer) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP, a neurodegenerative disease) after a long latency period as an asymp...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-021-01643-8 |
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| author | Mohadeseh Zarei Ghobadi Rahman Emamzadeh Majid Teymoori-Rad Sayed-Hamidreza Mozhgani |
| author_facet | Mohadeseh Zarei Ghobadi Rahman Emamzadeh Majid Teymoori-Rad Sayed-Hamidreza Mozhgani |
| author_sort | Mohadeseh Zarei Ghobadi |
| collection | DOAJ |
| description | Abstract Background Human T-cell Leukemia Virus type-1 (HTLV-1) is a retrovirus that causes two diseases including Adult T-cell Leukemia/Lymphoma (ATLL cancer) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP, a neurodegenerative disease) after a long latency period as an asymptomatic carrier (AC). There are no obvious explanations about how each of the mentioned diseases develops in the AC carriers. Finding the discriminative molecular factors and pathways may clarify the destiny of the infection. Methods To shed light on the involved molecular players and activated pathways in each state, differentially co-expressed modules (DiffCoEx) algorithm was employed to identify the highly correlated genes which were co-expressed differently between normal and ACs, ACs and ATLL, as well as ACs and HAM/TSP samples. Through differential pathway analysis, the dysregulated pathways and the specific disease-genes-pathways were figured out. Moreover, the common genes between the member of DiffCoEx and differentially expressed genes were found and the specific genes in ATLL and HAM/TSP were introduced as possible biomarkers. Results The dysregulated genes in the ATLL were mostly enriched in immune and cancer-related pathways while the ones in the HAM/TSP were enriched in immune, inflammation, and neurological pathways. The differential pathway analysis clarified the differences between the gene players in the common activated pathways. Eventually, the final analysis revealed the involvement of specific dysregulated genes including KIRREL2, RAB36, and KANK1 in HAM/TSP as well as LTB4R2, HCN4, FZD9, GRIK5, CREB3L4, TACR2, FRMD1, LHB, FGF3, TEAD3, GRIN2D, GNRH2, PRLH, GPR156, and CRHR2 in ATLL. Conclusion The identified potential prognostic biomarkers and therapeutic targets are proposed as the most important platers in developing ATLL or HAM/TSP. Moreover, the proposed signaling network clarifies the differences between the functional players in the activated pathways in ACs, ATLL, and HAM/TSP. |
| first_indexed | 2024-12-17T20:15:04Z |
| format | Article |
| id | doaj.art-e640f20eef75454b9639b13f32acf781 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-12-17T20:15:04Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-e640f20eef75454b9639b13f32acf7812022-12-21T21:34:08ZengBMCVirology Journal1743-422X2021-08-0118111210.1186/s12985-021-01643-8Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology studyMohadeseh Zarei Ghobadi0Rahman Emamzadeh1Majid Teymoori-Rad2Sayed-Hamidreza Mozhgani3Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of IsfahanDepartment of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of IsfahanDepartment of Virology, School of Public Health, Tehran University of Medical SciencesDepartment of Microbiology, School of Medicine, Alborz University of Medical SciencesAbstract Background Human T-cell Leukemia Virus type-1 (HTLV-1) is a retrovirus that causes two diseases including Adult T-cell Leukemia/Lymphoma (ATLL cancer) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP, a neurodegenerative disease) after a long latency period as an asymptomatic carrier (AC). There are no obvious explanations about how each of the mentioned diseases develops in the AC carriers. Finding the discriminative molecular factors and pathways may clarify the destiny of the infection. Methods To shed light on the involved molecular players and activated pathways in each state, differentially co-expressed modules (DiffCoEx) algorithm was employed to identify the highly correlated genes which were co-expressed differently between normal and ACs, ACs and ATLL, as well as ACs and HAM/TSP samples. Through differential pathway analysis, the dysregulated pathways and the specific disease-genes-pathways were figured out. Moreover, the common genes between the member of DiffCoEx and differentially expressed genes were found and the specific genes in ATLL and HAM/TSP were introduced as possible biomarkers. Results The dysregulated genes in the ATLL were mostly enriched in immune and cancer-related pathways while the ones in the HAM/TSP were enriched in immune, inflammation, and neurological pathways. The differential pathway analysis clarified the differences between the gene players in the common activated pathways. Eventually, the final analysis revealed the involvement of specific dysregulated genes including KIRREL2, RAB36, and KANK1 in HAM/TSP as well as LTB4R2, HCN4, FZD9, GRIK5, CREB3L4, TACR2, FRMD1, LHB, FGF3, TEAD3, GRIN2D, GNRH2, PRLH, GPR156, and CRHR2 in ATLL. Conclusion The identified potential prognostic biomarkers and therapeutic targets are proposed as the most important platers in developing ATLL or HAM/TSP. Moreover, the proposed signaling network clarifies the differences between the functional players in the activated pathways in ACs, ATLL, and HAM/TSP.https://doi.org/10.1186/s12985-021-01643-8HTLV-1ACsATLLHAM/TSPDifferentially co-expressed modulesPathogenesis |
| spellingShingle | Mohadeseh Zarei Ghobadi Rahman Emamzadeh Majid Teymoori-Rad Sayed-Hamidreza Mozhgani Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study Virology Journal HTLV-1 ACs ATLL HAM/TSP Differentially co-expressed modules Pathogenesis |
| title | Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study |
| title_full | Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study |
| title_fullStr | Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study |
| title_full_unstemmed | Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study |
| title_short | Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study |
| title_sort | decoding pathogenesis factors involved in the progression of atll or ham tsp after infection by htlv 1 through a systems virology study |
| topic | HTLV-1 ACs ATLL HAM/TSP Differentially co-expressed modules Pathogenesis |
| url | https://doi.org/10.1186/s12985-021-01643-8 |
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