The effects of different HIV type 1 strains on human thymic function.
The effects of different HIV type 1 strains on human thymic function.
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不同 1 型 HIV 毒株对人类胸腺功能的影响。
DOI：
10.1089/088922202320886280
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kirschner,DeniseE
中科院分区：
文献类型：
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作者：
Ye,Ping;Kourtis,AthenaP;Kirschner,DeniseE
对 HIV-1 感染者的研究表明，胸腺可以被 HIV-1 感染。其中一些患者的 CD4+T 细胞显着下降，疾病进展更快。这种现象在严重依赖胸腺产生新 T 细胞的儿科患者中更为明显。我们假设 HIV-1 会导致胸腺内 T 细胞再生失败，这对疾病进展产生深远影响。基于我们已建立的人类胸腺生成模型，我们纳入了不同 HIV-1 毒株（R5 和 X4）与胸腺细胞之间的动态相互作用。我们的结果预测，不同 HIV-1 毒株的胸腺感染会不同程度地诱发胸腺功能障碍，从而导致 HIV-1 感染儿童和成人中观察到的疾病进展差异。 儿童胸腺感染比成人更严重，特别是在 X4 感染期间。这一结果可能是由于儿科患者的病毒载量较高且胸腺更加活跃。我们的结果还表明，病毒株从 R5 转换为 X4 会导致胸腺生成进一步恶化。我们预测病毒和宿主因素在控制胸腺感染中发挥着关键作用，包括菌株毒力和胸腺的健康状况。
Studies of HIV-1-infected humans indicate that the thymus can be infected by HIV-1. In some of these patients, there is a significant CD4+T cell decline and a faster disease progression. This phenomenon is more evident in pediatric patients who depend heavily on their thymus for generation of new T cells. We hypothesize that HIV-1 causes T cell regenerative failure within the thymus, which has a profound impact on disease progression. Building on our established human thymopoiesis model, we include dynamic interactions between different HIV-1 strains (R5 and X4) and thymocytes. Our results predict that thymic infection with different HIV-1 strains induces thymic dysfunction to varying degrees, contributing to differences in disease progression as observed in both HIV-1-infected children and adults. Thymic infection in children is more severe than in adults, particularly during X4 infection. This outcome is likely due to both a higher viral load and a more active thymus in pediatric patients. Our results also indicate that a viral strain switch from R5 to X4 induces further deterioration in thymopoiesis. We predict that both viral and host factors play key roles in controlling thymic infection, including strain virulence and health status of the thymus.