Department of Clinical Sciences, University of Milano, Milano, Italy.
Blood. 2012 Jun 28;119(26):6259-67. doi: 10.1182/blood-2011-09-379503. Epub 2012 Jan 27.
MicroRNAs (miRNAs) inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4(+) T cells from HIV-1 élite long-term nonprogressors (éLTNPs), naive patients, and multiply exposed uninfected (MEU) patients, and we observed that the éLTNP patients clustered with naive patients, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated éLTNP from MEU patients and 23 miRNAs distinguished naive from MEU patients, whereas only 1 miRNA (miR-155) discriminated éLTNP from naive patients. We proposed that miRNA expression may discriminate between HIV-1-infected and -exposed but negative patients. Analysis of miRNAs expression after exposure of healthy CD4(+) T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro condition revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway.
微小 RNA（miRNA）通过调节宿主固有免疫或直接干扰病毒 mRNA 来抑制 HIV-1 的表达。我们评估了 CD4(+)T 细胞中 377 个 miRNA 在 HIV-1 精英长期非进展者（éLTNPs）、未感染患者和多次暴露未感染（MEU）患者中的表达，我们观察到 éLTNP 患者与未感染患者聚类，而所有 MEU 患者聚集在一起。miRNA 的区分能力表明，21 个 miRNA 显著区分了 éLTNP 与 MEU 患者，23 个 miRNA 区分了未感染与 MEU 患者，而只有 1 个 miRNA（miR-155）区分了 éLTNP 与未感染患者。我们提出 miRNA 表达可能区分 HIV-1 感染和暴露但阴性的患者。分析健康 CD4(+)T 细胞在体外暴露于 gp120 后 miRNA 的表达证实了我们的假设，即 miRNA 谱不仅是由于产生性感染，而且是由于暴露于 HIV-1 产物而产生的，这些产物在免疫细胞中留下了特征。在体外和体内条件下比较归一化的 Dicer 和 Drosha 表达表明，这些酶不会影响 miRNA 谱的变化，支持存在一种非 Dicer 依赖性生物发生途径。
