MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression. We aimed to determine the association between extracellular miRNAs and HIV infection.
Single-center, cross-sectional study.
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.
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.
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.
*Division of Cardiology and the Center of Excellence in Vascular Research, San Francisco General Hospital, University of California, San Francisco, CA;
†Cardiovascular Research Institute, University of California, San Francisco, CA;
‡Division of Cardiology, University of Massachusetts Medical School, Worcester, MA; and
§Department of Medicine, University of California, San Francisco, CA.
Correspondence to: Venkata Narla, MD, Box 1354, 500 Parnassus Avenue, MU Room E434, San Francisco, CA 94143 (e-mail: firstname.lastname@example.org).
Supported by Venkata Narla Grant Support: Center for AIDS Research (CFAR) Mentored Scientist Award, American College of Cardiology Merck Foundation Research Fellowship Award. Priscilla Hsue Grant Support: NIAID K24AI112393, NHLBI R01 HL095130; Priscilla Hsue has received honoraria from Gilead and grant support from Pfizer. Jane Freedman: UH2TR000921 and U01HL126495.
Presented at American College of Cardiology 2015 Scientific Sessions and at the Conference on Retroviruses and Opportunistic Infections (CROI) 2015.
The authors have no conflicts of interest to disclose.
V.N. contributed to data management, data analysis and interpretation, writing of manuscript, and critical revision of manuscript. N.B. contributed to data analysis and interpretation, and critical revision of manuscript. J.F. and K.T. contributed to data collection, data interpretation, and critical revision of manuscript. K.M. contributed to implementation of study, data management, and critical revision of manuscript. S.D. and P.G. contributed to critical revision of manuscript. P.H. contributed to study design and planning, implementation of study, data interpretation, writing of manuscript, and critical revision of manuscript.
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Received August 03, 2017
Accepted August 21, 2018