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?

Viruses. 2015 Oct 28;7(11):5643-58. doi: 10.3390/v7112897.

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.

Objectives: (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.

Keywords: HTLV-1/2; Western blot; indeterminate; mutations; proviral load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Argentina
  • Blotting, Western / methods*
  • Cross-Sectional Studies
  • Female
  • Gene Products, tax / genetics
  • HTLV-I Infections / diagnosis*
  • HTLV-I Infections / virology*
  • Human T-lymphotropic virus 1 / chemistry*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Proviruses / chemistry*
  • Retrospective Studies
  • Terminal Repeat Sequences
  • Viral Load*
  • Viral Proteins / analysis*
  • Young Adult

Substances

  • Gene Products, tax
  • Viral Proteins
  • tax protein, Human T-lymphotrophic virus 1