Comparative molecular analysis of HTLV-I proviral DNA in HTLV-I infected members of a family with a discordant HTLV-I-associated myelopathy in monozygotic twins

J Neurovirol. 2000 Aug;6(4):275-83. doi: 10.3109/13550280009030753.


In order to elucidate the underlying mechanisms of a discordant case with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in monozygotic twins, we investigated HTLV-I tax sequences of 10 - 18 polymerase chain reaction-based clones each derived from peripheral blood mononuclear cells of the twins as well as their infected mother and an elder brother who also suffered from HAM/TSP. Sequence comparison revealed that three of the infected individuals including a twin with HAM/TSP shared the consensus tax sequence identical to the reference, ATK-1, but that of another healthy twin was different at five nucleotide positions including three nonsynonymous changes from ATK-1. This finding strongly suggested that different HTLV-I strains infected the monozygotic twins and the difference in infected proviral sequences determined the discordant clinical outcomes. Transfection and subsequent reporter assays failed to show a significant difference in transactivation activity on HTLV-I LTR and NF-kappaB elements between the products of the two sequences. Two HAM/TSP patients (a twin and elder brother) among three members infected with the ATK-1 type virus shared a paternal HLA allele which was absent in the healthy individual (mother). Genetic analysis of sequence variation in the tax sequences of the discordant twins showed that the Dn/Ds ratio was high in the healthy twin but low in the twin with HAM/TSP, implying the presence of more intense selection forces in the carrier. Our findings strongly suggested that a particular combination of HTLV-I strains with an HLA genotype would be a risk for HAM/TSP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cloning, Molecular
  • Consensus Sequence
  • Diseases in Twins*
  • Female
  • Gene Products, tax / genetics
  • Genes, Viral*
  • Genetic Variation
  • Human T-lymphotropic virus 1 / genetics*
  • Human T-lymphotropic virus 1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Open Reading Frames
  • Paraparesis, Tropical Spastic / diagnosis
  • Paraparesis, Tropical Spastic / virology*
  • Pedigree
  • Proviruses / genetics*
  • Proviruses / isolation & purification
  • Risk Factors
  • Serotyping
  • Twins, Monozygotic
  • Viral Load


  • Gene Products, tax

Associated data

  • GENBANK/AB038239