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慢性阿片类药物给药后恒河猴免疫缺陷病毒感染的血浆蛋白质组变化。

Changes in the plasma proteome follows chronic opiate administration in simian immunodeficiency virus infected rhesus macaques.

机构信息

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5880, USA.

出版信息

Drug Alcohol Depend. 2012 Jan 1;120(1-3):105-12. doi: 10.1016/j.drugalcdep.2011.07.009. Epub 2011 Aug 6.

Abstract

BACKGROUND

Substantive plasma proteomic changes follow lentiviral infection and disease pathobiology. We posit that such protein alterations are modified during drug abuse, further serving to affect the disease. To this end, we investigated the effect of opiate administration on the plasma proteome of Indian-strain rhesus monkeys infected with simian immunodeficiency virus (SIV) strain smm9.

METHODS

Whole blood was collected at 7 weeks prior to and 1.4 and 49 weeks after viral infection. Viral load, CD4(+) T cell subsets, and plasma protein content were measured from monkeys that did or did not receive continuous opiate administrations. The plasma proteome was identified and quantified by isobaric tags for relative and absolute quantitation labeling (iTRAQ) and mass spectrometry.

RESULTS

While substantive changes in plasma proteins were seen during SIV infection, the addition of opiates led to suppression of these changes as well as increased variance of the proteome. These changes demonstrate that opiates induce broad but variant immune suppression in SIV-infected monkeys.

CONCLUSION

The broad suppressive changes seen in plasma of SIV-infected monkeys likely reflect reduced multisystem immune homeostatic responses induced by opiates. Such occur as a consequence of complex cell-to-cell interactions operative between the virus and the host. We conclude that such changes in plasma proteomic profiling may be underappreciated and as such supports the need for improved clinical definitions.

摘要

背景

慢病毒感染和疾病病理生物学会引起实质性的血浆蛋白质组变化。我们假设,在药物滥用期间,这些蛋白质变化会发生改变,从而进一步影响疾病。为此,我们研究了阿片类药物给药对感染 SIV 印度株的恒河猴血浆蛋白质组的影响,这些猴子都患有 SIV 感染。

方法

在病毒感染前 7 周、感染后 1.4 周和 49 周采集全血。对接受或未接受持续阿片类药物给药的猴子测量病毒载量、CD4(+) T 细胞亚群和血浆蛋白含量。通过相对和绝对定量标记(iTRAQ)和质谱法鉴定和定量血浆蛋白质组。

结果

虽然在 SIV 感染期间观察到血浆蛋白的实质性变化,但阿片类药物的添加导致这些变化被抑制,并且蛋白质组的变化增加。这些变化表明,阿片类药物在 SIV 感染的猴子中诱导广泛但不同的免疫抑制。

结论

SIV 感染猴子血浆中广泛的抑制性变化可能反映了阿片类药物诱导的多系统免疫稳态反应的减少。这些变化是病毒和宿主之间复杂的细胞间相互作用的结果。我们得出结论,血浆蛋白质组分析中的这些变化可能被低估了,因此需要改进临床定义。

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