Biobehavioral Nursing & Health Systems Department, University of Washington, School of Nursing, Seattle, WA 98195, USA.
Biol Res Nurs. 2013 Apr;15(2):137-51. doi: 10.1177/1099800411421957. Epub 2013 Jan 16.
Human immunodeficiency virus (HIV)-related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs).
The authors compared gene expression profiles of CD14(+) cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. RELEVANCE FOR NURSING PRACTICE: Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14(+) cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients.
The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction.
人类免疫缺陷病毒(HIV)相关疲劳(HRF)是多因素的,并且可能与抗逆转录病毒治疗核苷逆转录酶抑制剂(NRTIs)引起的线粒体功能障碍有关。
作者比较了低疲劳与高疲劳、接受 NRTI 治疗的 HIV 患者的 CD14+细胞与健康对照者(每组 n = 5)的基因表达谱。作者确定了 32 个可预测低疲劳与高疲劳的基因和 33 个可预测健康与 HIV 感染的基因。作者构建了遗传网络,以进一步阐明这些基因可能涉及的生物学途径。
包括肌动蛋白细胞骨架调节蛋白 Prokineticin 2 和 Cofilin 2 在内的基因以及线粒体内膜蛋白参与多个途径,是疲劳状态的预测因子。先前确定的炎症和信号基因可预测 HIV 状态,这清楚地证实了我们的结果,并表明线粒体功能与 HIV 之间可能存在进一步的联系。分离的 CD14+细胞是容易获得的细胞,可用于进一步研究 HIV 患者疲劳与线粒体功能之间的联系。
这项初步研究的结果使我们离确定疲劳状态和线粒体功能障碍的生物标志物靶标更近了一步。特定的生物标志物将与诊断、监测和治疗疲劳和线粒体功能障碍的方法的发展相关。