Polymorphisms in HTLV-1 Tax-responsive elements in HTLV-1-associated myelopathy/tropical spastic paraparesis patients are associated with reduced proviral load but not with disease progression

J Gen Virol. 2021 Sep;102(9). doi: 10.1099/jgv.0.001649.

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we evaluated polymorphisms in the 5' LTR and the association with PVL and disease progression. HTLV-1 LTR and tax sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5' TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.

Keywords: HAM/TSP; HTLV-1; genetic polymorphism; proviral load; tax-responsive elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asymptomatic Diseases
  • Carrier State / virology
  • Disease Progression
  • Female
  • Gene Products, tax*
  • Human T-lymphotropic virus 1 / genetics*
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation
  • Paraparesis, Tropical Spastic / virology*
  • Phylogeny
  • Polymorphism, Genetic*
  • Proviruses / genetics
  • Proviruses / physiology
  • Terminal Repeat Sequences*
  • Viral Load*

Substances

  • Gene Products, tax