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来自 HIV/HTLV-1 合并感染患者的 HTLV-1 分离株 Tax 反应元件中的 LTR 点突变。

LTR point mutations in the Tax-responsive elements of HTLV-1 isolates from HIV/HTLV-1-coinfected patients.

机构信息

Immunology Department, Instituto Adolfo Lutz, Av, Dr, Arnaldo, 355, 11° andar, São Paulo, SP, 01246-902, Brazil.

出版信息

Virol J. 2012 Sep 4;9:184. doi: 10.1186/1743-422X-9-184.

Abstract

BACKGROUND

In Virology Journal 2011, 8:535, Neto et al. described point mutations into Tax-responsive elements (TRE) of the LTR region of HTLV-1 isolates from asymptomatic carriers from Sao Paulo, Brazil, and hypothesized that the presence of the G232A mutation in the TRE-1 increase viral proliferation and consequently the proviral load (PvL), while the A184G mutation in the TRE-2 do not have such effect.

FINDINGS

We performed the real-time PCR assay (pol) and sequenced LTR region of HTLV-1 isolates from 24 HIV/HTLV-1-coinfected patients without HTLV-1-associated diseases from the same geographic area. These sequences were classified as belonging to the transcontinental subgroup A of the Cosmopolitan subtype a. The frequency of G232A mutation (16/24, 66.7%) was high as much as 61.8% reported by Neto's in HTLV-1 asymptomatic carriers with high PvL. High frequency (13/24, 54.2%) of double mutations G232A and A184G was also detected in HIV/HTLV-1-coinfected patients. We did not quantify PvL, but comparative analyses of the cycle threshold (Ct) median values of the group of isolates presenting the mutated-types sequences (Ct 33.5, n = 16) versus the group of isolates with the wild-type sequences (Ct 32, n = 8) showed no statistical difference (p = 0.4220).

CONCLUSION

The frequencies of mutated-type sequences in the TRE-1 and TRE-2 motifs were high in HIV/HTLV-1-coinfected patients from Sao Paulo, Brazil. If these LTR point mutations have predictive value for the development of HTLV-1-associated diseases or they correspond to the subtype of virus that circulate in this geographic area has to be determined.

摘要

背景

在 2011 年的《病毒学期刊》上,Neto 等人描述了巴西圣保罗无症状携带者的 HTLV-1 分离株中 LTR 区 Tax 反应元件(TRE)的点突变,并假设 TRE-1 中的 G232A 突变会增加病毒的增殖,从而增加前病毒载量(PvL),而 TRE-2 中的 A184G 突变则没有这种作用。

发现

我们对来自同一地理区域的 24 名 HIV/HTLV-1 合并感染且无 HTLV-1 相关疾病的患者的 HTLV-1 分离株进行了实时 PCR 检测(pol)和 LTR 区测序。这些序列被归类为属于世界性亚型 a 的跨大陆亚组 A。G232A 突变的频率(24 例中有 16 例,66.7%)与 Neto 等人报告的高 PvL 的 HTLV-1 无症状携带者中的 61.8%一样高。在 HIV/HTLV-1 合并感染患者中,还检测到 G232A 和 A184G 双重突变的高频(24 例中有 13 例,54.2%)。我们没有对 PvL 进行定量,但对携带突变型序列的分离株组(Ct 33.5,n=16)与携带野生型序列的分离株组(Ct 32,n=8)的中位 Ct 值进行比较分析,结果无统计学差异(p=0.4220)。

结论

巴西圣保罗的 HIV/HTLV-1 合并感染患者 TRE-1 和 TRE-2 序列的突变型序列频率较高。如果这些 LTR 点突变对 HTLV-1 相关疾病的发展具有预测价值,或者它们对应于该地理区域流行的病毒亚型,则需要进一步确定。

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