Fundação Pro-Sangue, Blood Center of São Paulo, São Paulo, Brazil.
Virol J. 2011 Dec 13;8:535. doi: 10.1186/1743-422X-8-535.
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.
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.
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).
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.
体外研究表明，在人类 T 细胞白血病病毒 I 型（HTLV-1）病毒启动子的每个 21 个碱基不完美重复的 Tax 反应元件（TRE）中引入缺失和点突变，可消除 Tax 的诱导。鉴于这些数据，我们假设类似的突变可能会影响 HTLV-1 感染细胞的增殖，并改变前病毒载量（PvL）。为了验证这一假设，我们进行了一项横断面遗传分析，以比较在具有不同 PvL 负担的 HTLV-1 无症状携带者样本中，覆盖 TRE1 区域的近乎完整 LTR 核苷酸序列。
共研究了 94 名 HTLV-1 无症状携带者，他们的 5'长末端重复（LTR）序列和 Tax DNA 的 PvL 均使用敏感的 SYBR Green 实时 PCR 进行了测量。根据 PvL 测量值，将 94 名受试者分为三组：31 名低、29 名中、34 名高。此外，还根据性别、年龄和病毒基因型对每组进行了比较。在另一项分析中，比较了感染突变型和野生型病毒个体之间的中位数 PvL。
使用分类分析，在低、中、高 PvL 组的受试者中，分别有 38.7%（12/31）、27.5%（8/29）和 61.8%（21/34）检测到位于 TRE-1 基序域 A 中的 G232A 取代。在高或低 PvL 受试者与高或中 PvL 受试者之间，以及在低或中 PvL 受试者之间，均发现该突变的检测存在显著差异（均 p < 0.05），但在低或中 PvL 受试者之间不存在差异（p > 0.05）。非参数分析也证实了这一结果，结果显示，与没有 G232A 突变的个体相比，G232A 突变的 HTLV-1 阳性个体的 PvL 明显更高（p < 0.03）。在年龄、性别或病毒亚型方面，各组之间无显著差异（p > 0.05）。
这里描述的数据表明，导致 G232A 突变的 HTLV-1 TRE-1 基序域 A 的变化可能会增加大多数感染个体中 HTLV-1 的复制。
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