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首页> 外文期刊>AIDS Research and Human Retroviruses >In vivo HIV-1 hypermutation and viral loads among antiretroviral-naive Brazilian patients
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In vivo HIV-1 hypermutation and viral loads among antiretroviral-naive Brazilian patients

机译：初次使用抗逆转录病毒的巴西患者体内的HIV-1高变和病毒载量

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Hypermutation alludes to an excessive number of specific guanine-to-adenine (G-A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4+ T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression.
机译：超突变暗示原病毒DNA中过量的特定鸟嘌呤-腺嘌呤（G-> A）取代，这种现象归因于细胞APOBEC的催化活性。已经进行了有关超突变和人类1型免疫缺陷病毒（HIV-1）感染进展的人群研究，以阐明超突变对HIV-1感染自然过程的影响。然而，用于评估核苷酸序列中的超突变的许多不同方法使得比较结果变得困难。这项研究选择了157位未接受过治疗的患者，并试图将临床样本中前病毒序列的超突变水平与人口统计学变量，HIV-1 RNA病毒载量和CD4 + T细胞水平相关联。使用特异性引物进行巢式触地聚合酶链反应（PCR），以检测HIV-1整合酶区域的超突变，并将扩增的序列在带有HA-Yellow的琼脂糖凝胶中电泳。通过k-均值聚类方法对凝胶迁移模式的分析已通过与Hypermut软件获得的结果相吻合而得到验证。在31.2％的调查样本中发现超突变，并且在较高的超突变水平和较高的病毒载量水平之间观察到相关性。这些发现表明，在巴西人群中进行高突变检测的频率很高，这可以反映该人群的特定特征，但也可以通过针对高突变敏感位点的方法来获得。此外，我们发现高病毒复制在HIV-1感染期间普遍存在超突变事件，这反映了其在疾病进展过程中的作用。

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