title: Correlation between LTR point mutations and proviral load levels among human T cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers.
abstract: BACKGROUND
  In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE) of the genuine human T-cell leukemia virus type I (HTLV-1) viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1-infected cells and alter the proviral load (PvL). To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden.
  
  
  METHODS
  A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR) and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared.
  
  
  RESULTS
  Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31), 27.5% (8/29), and 61.8% (21/34) of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p < 0.05), but not between subjects with a low or intermediate PvL (p > 0.05). This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p < 0.03). No significant difference was found between the groups in relation to age, sex or viral subtypes (p > 0. 05).
  
  
  CONCLUSIONS
  The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.
authors.affiliation: Fundação Pro-Sangue, Blood Center of São Paulo, São Paulo, Brazil.
authors.forename: Walter K
authors.initials: WK
authors.lastname: Neto
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Da-Costa
authors.forename: Ana Carolina S
authors.initials: AC
authors.lastname: de Oliveira
authors.forename: Vanessa P
authors.initials: VP
authors.lastname: Martinez
authors.forename: Youko
authors.initials: Y
authors.lastname: Nukui
authors.forename: Ester C
authors.initials: EC
authors.lastname: Sabino
authors.forename: Sabri S
authors.initials: SS
authors.lastname: Sanabani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002353:Carrier State / Q000503:physiopathology / Q000821:virology*; D003430:Cross-Sectional Studies; D005260:Female; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D016355:Genes, pX; D015490:HTLV-I Infections / Q000503:physiopathology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D020218:Response Elements; D020079:Terminal Repeat Sequences / Q000235:genetics*; D019562:Viral Load; D014779:Virus Replication; D055815:Young Adult
chemical_list: D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1