Systems Biology Approaches Reveal a Specific Interferon-Inducible Signature in HTLV-1 Associated Myelopathy
نویسندگان
چکیده
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.
منابع مشابه
P 130: The Role of Host T- Cell Lymphocyte in Immunopathogenesis of HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis
Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Only a limited percentage of infected individuals develop disease in response to the virus while the majority remain asymptomatic and HAM/TSP is the most common clinical manifestation of the virus. HAM/TSP is an inflamma...
متن کاملThe Impact of Immune Response on HTLV-I in HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
Human T lymphotropic virus type I (HTLV-I) is a retrovirus which is associated with adult T cells leukaemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of HTLV-I-infected individuals. It is not clear why a minority of HTLV-I-infected individuals develop HAM/TSP and majority remains lifelong carriers. It seems that the interaction between the v...
متن کاملInterferon Beta-1a Treatment in Htlv-1-associated Myelopathy/tropical Spastic Paraparesis: a Case Report
Here a young patient (< 21 years of age) with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and laboratory tests confirmed the presence of antibodies to ...
متن کاملInterferon- Gamma- Inducible Guanosine Triphosphate Cyclohydrolase 1 (GTP-CH1) Pathway Is Associated with Frailty in Egyptian Elderly
Background: Chronic low-grade inflammation may be a cardinal pathophysiologic feature in the pathogenesis of frailty. Interferon-gamma (INF-γ) is an understudied proinflammatory cytokine in frailty that induces many inflammatory pathways including the guanosine triphosphate cyclohydrolase 1 (GTP-CH1) pathway. Our aim was to evaluate the GTP-CH1 pathway in Egyptian frail elderly subjects. ...
متن کامل