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 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. © 2012 tattermusch et al.