title: High IFN-γ/IL-10 expression ratio and increased frequency of persistent human T-cell lymphotropic virus type 1-infected clones are associated with human T-cell lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis development.
abstract: OBJECTIVE
  Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes a persistent infection, and only 0.5-5% of infected individuals will develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Therefore, we investigated parameters to discriminate HTLV-1 asymptomatic carriers (ACs) with an increased chance to develop HAM/TSP.
  
  
  METHODS
  We evaluated integration patterns of HTLV-1 provirus, the relative expression of HTLV-1 tax and HBZ mRNAs and of IFN-γ and IL-10 mRNAs, in addition to proviral load (PVL) levels.
  
  
  RESULTS
  HAM/TSP patients presented a higher number of large persistent HTLV-1-carrying clones compared to ACs, and the expression of the HTLV-1 tax and HBZ genes by infected cells was detected at low levels and correlated positively with PVL. In addition, HAM/TSP patients and ACs with high PVL expressed higher levels of IFN-γ mRNA in comparison to IL-10, while ACs with low PVL presented an equilibrate IFN-γ/IL-10 ratio.
  
  
  CONCLUSIONS
  The presence of large persistent HTLV-1-infected clones in association with viral gene expression, even at small levels, could stimulate the intense inflammatory response in HTLV-1-infected individuals. This was supported by a high ratio of IFN-γ/IL-10 relative expression in HAM/TSP patients and ACs with high PVL, indicating that these parameters could aid the identification of ACs with a high risk to develop HAM/TSP.
authors.affiliation: Laboratory for Research on Viral Pathogenesis, Evandro Chagas National Institute of Infectious Diseases - FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Otávio M
authors.initials: OM
authors.lastname: Espíndola
authors.forename: Luã C
authors.initials: LC
authors.lastname: Oliveira
authors.forename: Priscilla M S
authors.initials: PM
authors.lastname: Ferreira
authors.forename: Ana Claudia C B
authors.initials: AC
authors.lastname: Leite
authors.forename: Marco Antonio S D
authors.initials: MA
authors.lastname: Lima
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Andrada-Serpa
mesh_terms: D000328:Adult; D058345:Asymptomatic Infections; D015415:Biomarkers; D005260:Female; D005814:Genes, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D015493:Paraparesis, Tropical Spastic / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D015415:Biomarkers; D016753:Interleukin-10; D007371:Interferon-gamma