Correlation between LTR point mutations and proviral load levels among Human T cell Lymphotropic Virus type 1 (HTLV-1) asymptomatic carriers

Author(s)

Neto, Walter K. ^{[1, 2]} ; Da-Costa, Antonio C. ^{[1, 3]} ; de Oliveira, Ana Carolina S. ^{[1, 3]} ; Martinez, Vanessa P. ^[4] ; Nukui, Youko ^[2] ; Sabino, Ester C. ^[5] ; Sanabani, Sabri S. ^{[1, 3]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Translat Med, Sao Paulo - Brazil

^[2] Fundacao Prosangue, Blood Ctr Sao Paulo, Sao Paulo - Brazil

^[3] Sao Paulo Inistitute Trop Med, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Retrovirol Lab, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Dept Infect Dis, Sao Paulo - Brazil

• Document type: Journal article
• Source: VIROLOGY JOURNAL; v. 8, DEC 13 2011.
• Web of Science Citations: 6

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. (AU)

• FAPESP's process: 10/08550-1 - T cell clonal expansion and proviral load levels among human t cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers
• Grantee: Ester Cerdeira Sabino
• Support Opportunities: Regular Research Grants