MicroRNA-150 Is a Potential Biomarker of HIV/AIDS Disease Progression and Therapy

Abstract

BackgroundThe surrogate markers of HIV/AIDS progression include CD4 T cell count and plasma viral load. But, their reliability has been questioned in patients on anti-retroviral therapy (ART). Five microRNAs (miRNAs) - miR-16, miR-146b-5p, miR-150, miR-191 and miR-223 in peripheral blood mononuclear cells (PBMCs) were earlier found to assign HIV/AIDS patients into groups with varying CD4 T cell counts and viral loads. In this pilot study, we profiled the expression of these five miRNAs in PBMCs, and two of these miRNAs (miR-146b-5p and miR-150) in the plasma of HIV/AIDS patients, including those on ART and those who developed ART resistance, to evaluate if these are biomarkers of disease progression and therapy.ResultsWe quantified miRNA levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RNA isolated from PBMCs and plasma of healthy persons or HIV-infected patients who were (1) asymptomatic; (2) symptomatic and ART naïve; (3) on ART; and (4) failing ART. Our results show miR-150 (p<0.01) and to a lesser extent miR-146b-5p (p<0.05) levels in PBMCs to reliably distinguish between ART-naïve AIDS patients, those on ART, and those developing drug resistance and failing ART. The plasma levels of these two miRNAs also varied significantly between patients in these groups and between patients and healthy controls (p values <0.05).ConclusionsWe report for the first time that PBMC and plasma levels of miR-150 and miR-146b-5p are predictive of HIV/AIDS disease progression and therapy.

MicroRNA and HIV

“…It has been observed that HIV infection causes changes in the profile of some miRNA such as miR-29a, miR-29b, miR-125b, miR-223, miR-382, miR-198, etc. This changes have been observed in infected CD4 + T cell, PBMCs or serum [1][2][3]6,[8][9][10][19][20][21]. However, it should be taken into account that miRNAs may be regulated in different ways providing different profiles depending on the different immune compartments.…”

“…Editorial microRNAs (miRNAs) are non-coding RNAs (19-25 nucleotides) that regulate gene expression at transcriptional level [1][2][3][4][5][6]. They bind to messenger RNAs (mRNA), generally by imperfect base alignment in 3'-UTR region, and cause translational repression, mRNA destabilization and/or mRNA direct destruction [3][4][5].…”

“…It has been described that miRNAs can induce heterochromatin formation as well as it can induce protein translations sometimes [4]. There are over 2500 annotated and more than 60% of human genes are regulated by them [1,3,4]. A particular miRNA can regulate multiple mRNAs.…”

“…However, it should be taken into account that miRNAs may be regulated in different ways providing different profiles depending on the different immune compartments. For example, miR-150 in HIV infected patients is much higher in plasma than in the cell compartments [1]. Cellular miRNA play a critical role in the pathogenesis of HIV intervening in viral infection, latency and mediating cell intrinsic resistance [6,10,19].…”

“…In plants, invertebrates and mammals it has been described that miRNAs play a crucial role in innate antiretroviral defense [10]. There are few described miRNAs having a direct effect on the virus but large numbers of them affect HIV indirectly throughout the regulation of factors that are necessary for viral cycle [1,2,6,[8][9][10]19,21].…”