Cytopenias in HIV infection: Mechanisms and alleviation of hematopoietic inhibition
Cytopenias in HIV infection: Mechanisms and alleviation of hematopoietic inhibition
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DOI：
10.2174/1570162043351282
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发表时间：
2004-07-01
影响因子：
1
通讯作者：
Reddy, ST
中科院分区：
文献类型：
--
作者：
Koka, PS;Reddy, ST
HIV感染者常出现造血功能异常，包括贫血、血细胞减少和骨髓微环境中干细胞可塑性的改变。这些观察结果表明，HIV-1感染可能会影响造血或干细胞分化早期阶段的重要过程。造血异常可能是由于某些细胞基因（如与造血相关的细胞因子）的异常谱系特异性表达导致的干细胞分化改变所致。这些细胞因子可以影响造血中重要的调节信号。然而，在HIV感染的个体中，不仅病毒而且高效抗逆转录病毒疗法（HAART）都有助于持续的造血抑制和随后的血细胞减少。即使在感染个体中发生HAART降低HIV复制，延长HAART本身和/或耐药突变体的出现也会导致造血抑制和导致血细胞减少。然而，混杂因素，如机会性感染，免疫介导的影响，或长期的生理应激的后果，这可能有助于减少患者或其他个体的造血，使艾滋病毒在体内的致病作用，不确定。严重联合免疫缺陷小鼠移植人胎胸腺和肝组织（SCID-hu）是一种模拟人类HIV感染的小动物模型，对研究HIV-1诱导的造血抑制机制和开发干预造血干细胞分化的药物治疗具有重要意义。此外，SCID小鼠作为人类祖细胞的有用的小动物受体，也使我们能够研究这些细胞在体内的分化。我们的研究结果有望缓解HIV感染者的造血抑制和随后的血细胞减少。
Hematopoietic abnormalities including anemia, cytopenias, and alterations of the stein cell plasticity in the bone marrow microenvironment commonly occur in HIV infected patients. These observations suggest that HIV-1 infection may affect processes important during early stages of hematopoiesis or stem cell differentiation. Hematopoietic abnormalities may be caused by altered stein cell differentiation possibly due to abnormal lineage specific expression of certain cellular genes such as cytokines relevant to hematopoiesis. These cytokines could affect regulatory signals important in hematopoiesis. However, in HIV infected individuals, it is not only the virus but also the highly active antiretroviral therapy (HAART) that both contribute to persistent hematopoietic suppression and ensuing cytopenias. Even if a lowering of HIV replication by HAART were to occur in infected individuals, prolonged HAART by itself and/or appearance of drug resistant mutants can contribute to hematopoietic suppression and resulting cytopenias. However, confounding factors such as opportunistic infections, immune mediated effects, or the consequences of prolonged physiological stress, which could contribute to decreased hematopoiesis in patients or other individuals, make the causative role of HIV in Vivo, uncertain. The severe combined immunodeficient mouse transplanted with human fetal thymus and liver tissues (SCID-hu) is a small animal model which mimics HIV infection in humans, and is useful to determine the mechanisms of HIV-1 induced hematopoietic inhibition and development of drug therapies for interventions of stein cell differentiation. Further, SCID mouse serves as a useful small animal recipient of human progenitor cells and also allows us to study the differentiation of these cells in vivo. Results from our studies are expected to provide relief for HIV infected individuals from hematopoietic inhibition and ensuing cytopenias.