Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown a...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002480&type=printable |
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| author | Sonja Tattermusch Jason A Skinner Damien Chaussabel Jacques Banchereau Matthew P Berry Finlay W McNab Anne O'Garra Graham P Taylor Charles R M Bangham |
| author_facet | Sonja Tattermusch Jason A Skinner Damien Chaussabel Jacques Banchereau Matthew P Berry Finlay W McNab Anne O'Garra Graham P Taylor Charles R M Bangham |
| author_sort | Sonja Tattermusch |
| collection | DOAJ |
| description | Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown and treatment remains ineffective. We used gene expression microarrays followed by flow cytometric and functional assays to investigate global changes in blood transcriptional profiles of HTLV-1-infected and seronegative individuals. We found that perturbations of the p53 signaling pathway were a hallmark of HTLV-1 infection. In contrast, a subset of interferon (IFN)-stimulated genes was over-expressed in patients with HAM/TSP but not in asymptomatic HTLV-1 carriers or patients with the clinically similar disease multiple sclerosis. The IFN-inducible signature was present in all circulating leukocytes and its intensity correlated with the clinical severity of HAM/TSP. Leukocytes from patients with HAM/TSP were primed to respond strongly to stimulation with exogenous IFN. However, while type I IFN suppressed expression of the HTLV-1 structural protein Gag it failed to suppress the highly immunogenic viral transcriptional transactivator Tax. We conclude that over-expression of a subset of IFN-stimulated genes in chronic HTLV-1 infection does not constitute an efficient host response but instead contributes to the development of HAM/TSP. |
| format | Article |
| id | doaj-art-9568bf840c1c48c092a25eeccf3a9c12 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-9568bf840c1c48c092a25eeccf3a9c122025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0181e100248010.1371/journal.ppat.1002480Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.Sonja TattermuschJason A SkinnerDamien ChaussabelJacques BanchereauMatthew P BerryFinlay W McNabAnne O'GarraGraham P TaylorCharles R M BanghamHuman T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown and treatment remains ineffective. We used gene expression microarrays followed by flow cytometric and functional assays to investigate global changes in blood transcriptional profiles of HTLV-1-infected and seronegative individuals. We found that perturbations of the p53 signaling pathway were a hallmark of HTLV-1 infection. In contrast, a subset of interferon (IFN)-stimulated genes was over-expressed in patients with HAM/TSP but not in asymptomatic HTLV-1 carriers or patients with the clinically similar disease multiple sclerosis. The IFN-inducible signature was present in all circulating leukocytes and its intensity correlated with the clinical severity of HAM/TSP. Leukocytes from patients with HAM/TSP were primed to respond strongly to stimulation with exogenous IFN. However, while type I IFN suppressed expression of the HTLV-1 structural protein Gag it failed to suppress the highly immunogenic viral transcriptional transactivator Tax. We conclude that over-expression of a subset of IFN-stimulated genes in chronic HTLV-1 infection does not constitute an efficient host response but instead contributes to the development of HAM/TSP.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002480&type=printable |
| spellingShingle | Sonja Tattermusch Jason A Skinner Damien Chaussabel Jacques Banchereau Matthew P Berry Finlay W McNab Anne O'Garra Graham P Taylor Charles R M Bangham Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. PLoS Pathogens |
| title | Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. |
| title_full | Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. |
| title_fullStr | Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. |
| title_full_unstemmed | Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. |
| title_short | Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. |
| title_sort | systems biology approaches reveal a specific interferon inducible signature in htlv 1 associated myelopathy |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002480&type=printable |
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