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

• Published in: Virology journal Vol. 8; no. 1; p. 535
• Main Authors: Neto, Walter K, Da-Costa, Antonio C, de Oliveira, AnaCarolina S, Martinez, Vanessa P, Nukui, Youko, Sabino, Ester C, Sanabani, Sabri S
• Format: Journal Article
• Language: English
• Published: London BioMed Central 13.12.2011; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Carrier State - physiopathology; Carrier State - virology; Colleges & universities; Cross-Sectional Studies; Design; DNA; domain; Female; Gene expression; Gene mutations; Gene Products, tax - genetics; Gene Products, tax - metabolism; Genes, pX; genetic analysis; Genetic aspects; Genomes; HTLV-I (Virus); HTLV-I Infections - physiopathology; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - physiology; Humans; Leukemia; Male; Middle Aged; mutants; Mutation; Nucleotide sequence; Point Mutation; Proteins; Proviruses - genetics; Proviruses - physiology; quantitative polymerase chain reaction; Response Elements; T-lymphocytes; terminal repeat sequences; Terminal Repeat Sequences - genetics; Viral Load; Virology; Virus Replication; viruses; Young Adult; Brazil; Long Terminal Repeat Region; Cosmopolitan Subtype; G232A Mutation; Proviral Load; Long Terminal Repeat
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-8-535

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-1i nfected 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.