Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium.
Retrovirology. 2010 Jun 14;7:53. doi: 10.1186/1742-4690-7-53.
During HIV infection and/or antiretroviral therapy (ART), monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions.
Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19) for the development of the abacavir hypersensitivity reaction were suggested.
Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV.
在 HIV 感染和/或抗逆转录病毒治疗（ART）期间，单核细胞和巨噬细胞表现出广泛的功能障碍，这对 HIV 发病机制和治疗相关并发症有重要贡献。然而，导致这些功能障碍的分子成分仍不清楚。因此，我们采用全基因组微阵列分析和聚焦基因表达谱的平行方法，对处于不同 HIV 感染和/或 ART 阶段的患者的单核细胞进行研究，以进一步描述这些功能障碍。
在 HIV 感染期间，凋亡、细胞周期、脂质代谢、蛋白酶体功能、蛋白质转运和转录调控等过程被确定为单核细胞功能障碍的相关过程。可能导致这些单核细胞功能障碍的个别基因包括几个新的因素。其中之一是脂肪细胞因子 NAMPT/visfatin，我们发现它能够在 HIV 生命周期的早期抑制 HIV。在 ART 下，大约一半的基因被恢复到对照水平，而其余的则代表持续的失调。此外，还提出了几种候选生物标志物（特别是 CCL1 和 CYP2C19）来预测阿巴卡韦过敏反应的发生。
证实了之前描述的 HIV 感染期间单核细胞功能障碍的领域，并确定了新的主题。此外，还确定了与这些功能障碍和与 ART 相关的疾病相关的个别基因。这些基因为进一步研究单核细胞/巨噬细胞对 HIV 发病机制的贡献提供了有用的基础。其中一个基因，NAMPT/visfatin，代表了 HIV 的一个可能的新限制因素。
