Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy

Sonja Tattermusch, Jason A. Skinner, Damien J. Chaussabel, Jacques Banchereau, Matthew P. Berry, Finlay W. McNab, Anne O'Garra, Graham P. Taylor, Charles R M Bangham

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Abstract

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.

Original languageEnglish
Article numbere1002480
JournalPLoS Pathogens
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Tattermusch, S., Skinner, J. A., Chaussabel, D. J., Banchereau, J., Berry, M. P., McNab, F. W., O'Garra, A., Taylor, G. P., & Bangham, C. R. M. (2012). Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. PLoS Pathogens, 8(1), [e1002480]. https://doi.org/10.1371/journal.ppat.1002480