Unique Circulating MicroRNA Profiles in HIV Infection

Abstract

OBJECTIVE: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression. We aimed to determine the association between extracellular miRNAs and HIV infection. DESIGN: Single-center, cross-sectional study. METHODS: We analyzed the expression of 192 plasma-derived miRNAs in 69 HIV-infected individuals and 24 uninfected controls using TaqMan miRNA assays and a high-throughput Real-Time PCR instrument (Fluidigm). False discovery rate (FDR) was applied. RESULTS: HIV-infected individuals and controls were similar in age, sex, and traditional risk factors. Among those with HIV, 72.5% were on antiretroviral therapy (ARVs) and 64% had an undetectable viral load. Twenty-nine miRNAs were differentially expressed in the plasma of HIV-infected individuals compared with controls (P < 0.05, FDR < 0.15). Nineteen miRNAs were differentially expressed among HIV+ subjects on ARVs, HIV+ subjects not on ARVs, and HIV- subjects (P < 0.05 and FDR < 0.15). Thirty-four miRNAs were differentially expressed between HIV- subjects and elite controllers (ie, suppressed viral loads despite the absence of ARVs; P < 0.05 and FDR < 0.15). These 34 miRNAs included miRs-29c, 146b, 223, and 382, which were previously reported to have intracellular roles in HIV latency, as well as miRs-126, 145, and let-7, which were previously shown to be differentially expressed in coronary artery disease among uninfected individuals. CONCLUSIONS: We demonstrate a unique expression profile of 29 miRNAs in HIV+ subjects and 34 miRNAs in elite controllers as compared to HIV- subjects. These miRNA signatures may be useful in further elucidating mechanisms of viral and immunological control and may have diagnostic or prognostic value in HIV-associated coronary artery disease.