| Texto completo | |
| Autor(es): |
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]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [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
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | VIROLOGY JOURNAL; v. 8, DEC 13 2011. |
| Citações Web of Science: | 6 |
| Resumo | |
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) | |
| Processo FAPESP: | 10/08550-1 - Expansão clonal de células T e níveis de carga proviral entre portadores assintomáticos de HTLV-1 |
| Beneficiário: | Ester Cerdeira Sabino |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |