title: Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?
abstract: BACKGROUND
  indeterminate Western blot (WB) patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) infection, even in non-endemic areas.
  
  
  OBJECTIVE
  (a) to define the prevalence of indeterminate WB among different populations from Argentina; (b) to evaluate if low proviral load (PVL) is associated with indeterminate WB profiles; and (c) to describe mutations in LTR and tax sequence of these cases.
  
  
  RESULTS
  Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3%) were WB indeterminate and of those 15 (31.3%) were PCR+. Quantitative real-time PCR (qPCR) was performed to 52 HTLV-1+ samples, classified as Group 1 (G1): 25 WB+ samples from individuals with pathologies; Group 2 (G2): 18 WB+ samples from asymptomatic carriers (AC); and Group 3 (G3): 9 seroindeterminate samples from AC. Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed. Age and sex were associated with PVL in G1 and G2, respectively. Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03).
  
  
  CONCLUSIONS
  indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels. Mutations in LTR and tax are described; their functional relevance remains to be determined.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. canepa.camila@gmail.com.
authors.forename: Camila
authors.initials: C
authors.lastname: Cánepa
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. jimenasalido@gmail.com.
authors.forename: Jimena
authors.initials: J
authors.lastname: Salido
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. ruggierimatias50@gmail.com.
authors.forename: Matías
authors.initials: M
authors.lastname: Ruggieri
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. sfraile77@gmail.com.
authors.forename: Sindy
authors.initials: S
authors.lastname: Fraile
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. gaby.pataccini@hotmail.com.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pataccini
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. cberini@fmed.uba.ar.
authors.forename: Carolina
authors.initials: C
authors.lastname: Berini
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Paraguay 2155, piso 11, C1121ABG, CABA, Argentina. mbiglione@fmed.uba.ar.
authors.forename: Mirna
authors.initials: M
authors.lastname: Biglione
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001118:Argentina; D015153:Blotting, Western / Q000379:methods*; D003430:Cross-Sectional Studies; D005260:Female; D016356:Gene Products, tax / Q000235:genetics; D015490:HTLV-I Infections / Q000175:diagnosis* / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011533:Proviruses / Q000737:chemistry*; D012189:Retrospective Studies; D020079:Terminal Repeat Sequences; D019562:Viral Load; D014764:Viral Proteins / Q000032:analysis*; D055815:Young Adult
chemical_list: D016356:Gene Products, tax; D014764:Viral Proteins; C514970:tax protein, Human T-lymphotrophic virus 1
keywords: HTLV-1/2; Western blot; indeterminate; mutations; proviral load