Interferon Lambda Family along with HTLV-1 Proviral Load, Tax, and HBZ Implicated in the Pathogenesis of Myelopathy/Tropical Spastic Paraparesis

Neurodegener Dis. 2018;18(2-3):150-155. doi: 10.1159/000490058. Epub 2018 Jul 10.

Abstract

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease related to human T lymphotropic virus type 1 (HTLV-1) infection. Interferon type III (IFN-λ), which includes IL28, IL29, and IL28R, and affects the outcome of viral infections, might be complicated in the progression of HAM/TSP. Here, we investigated the host-virus interactions in the manifestation of HAM/TSP, using IL28B, IL29, IL28R, HTLV-1 Tax, HTLV-1 basic leucine zipper factor (HBZ), and proviral load (PVL). The study groups consisted of 20 patients with HAM/TSP, 20 asymptomatic HTLV-1 carriers (ACs), and 20 healthy controls (HCs). The means of PVL, Tax, and HBZ gene expressions in the HAM/TSP group (p = 0.004, 0.006, and < 0.0001, respectively) were significantly higher than in the AC group. The comparison of IL28B, IL29, and IL28R expression in the HAM/TSP, AC, and HC groups revealed no significant difference between the first 2, but lower concentrations in the HCs (IL28B: p = 0.03, 0.01; IL29: p = 0.07, 0.01; and IL28R: p < 0.0001, respectively). In the HAM/TSP group, correlations were seen between Tax and HBZ (R = 0.61, p = 0.004) and between Tax and IL29 (R = 0.45, p = 0.04). Negative correlations were observed between Tax and IL28B (R = -0.49, p = 0.02) and between HBZ and IL28R (R = -0.43, p = 0.06). In the ACs, an inverse correlation was found between Tax and IL28B (R = -0.42, p = 0.06). These findings suggest that IL29, IL28B, and IL28R interfere in the infection of HAM/TSP, mainly via Tax activation.

Keywords: HTLV-1-associated myelopathy/tropical spastic paraparesis; Human T lymphotropic virus type 1; Interferon lambda.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Female
  • Genes, pX / genetics*
  • Human T-lymphotropic virus 1 / pathogenicity*
  • Humans
  • Interferon Lambda
  • Interferons / metabolism
  • Interleukins / metabolism*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Paraparesis, Tropical Spastic / virology
  • Proviruses / pathogenicity
  • Receptors, Cytokine / metabolism*
  • Receptors, Interferon
  • Retroviridae Proteins / metabolism*
  • Young Adult

Substances

  • Basic-Leucine Zipper Transcription Factors
  • HBZ protein, human T-cell leukemia virus type I
  • interferon-lambda, human
  • IFNLR1 protein, human
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interferon
  • Retroviridae Proteins
  • Interferons
  • Interferon Lambda