Background: Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments.Objectives. To define whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN.Design/Methods: An HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vectors (rAd-Tat). rAd-Tat and LacZ control vectors (2 x 10⁹) were expressed in the kidney of newborn wild type and HIV-transgenic (Tg₂₆) FVB/N mice without significant proteinuria (n=5 - 8 per group). Mice were sacrificed 7 and 35 days later to assess their renal outcome, the expression of HIV-genes and growth factors, and markers of cell growth and differentiation by RT-qPCR, immunohistochemistry, and/or Western blots.Results: HIV-Tat induced the expression of HIV-1 genes (env) and heparin binding growth factors in the kidney of HIV-Tg₂₆ mice, and precipitated HIVAN in the first month of life. No significant renal changes were detected in wild type mice infected with rAd-Tat vectors, suggesting that HIV-Tat alone does not induce renal disease.Conclusion This new mouse model of childhood HIVAN highlights the critical role that HIV-Tat plays in the pathogenesis of HIVAN, and could be used to study the pathogenesis and treatment of HIVAN in children and adolescents.

中文翻译：

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儿童 HIV 相关肾病的 HIV-Tat 诱导小鼠模型系统。

背景：现代抗逆转录病毒疗法 (ART) 降低了 HIV 相关肾病 (HIVAN) 的患病率。尽管如此，我们仍然在世界各地看到感染艾滋病毒的儿童和青少年。此外，HIVAN一旦在儿童中形成，就很难逆转其长期进展，我们需要更好的儿童HIVAN动物模型来测试新的治疗方法。目标。确定 HIV-1 反式激活子 (Tat) 基因是否会在幼年小鼠中引发 HIVAN，并开发儿童 HIVAN 的诱导型小鼠模型。设计/方法：使用从 HIVAN 儿童身上克隆的 HIV-Tat 基因来生成重组腺病毒载体 (rAd-Tat)。rAd-Tat 和LacZ对照载体 (2 x 10 ^{9 ) 在新生野生型和 HIV 转基因 (Tg} ₂₆ ) FVB/N 小鼠的肾脏中表达，无明显蛋白尿（每组 n=5 - 8）。7 天和 35 天后处死小鼠，通过 RT-qPCR、免疫组织化学和/或蛋白质印迹评估其肾脏结果、HIV 基因和生长因子的表达以及细胞生长和分化的标记。结果： HIV-Tat 诱导 HIV-Tg ₂₆小鼠肾脏中 HIV -1 基因 ( env ) 和肝素结合生长因子的表达，并在生命第一个月内引发 HIVAN。在感染 rAd-Tat 载体的野生型小鼠中没有检测到显着的肾脏变化，这表明单独的 HIV-Tat 不会诱发肾脏疾病。结论这种新的儿童HIVAN小鼠模型凸显了HIV-Tat在HIVAN发病机制中的关键作用，可用于研究儿童和青少年HIVAN的发病机制和治疗。