HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA–455-3p induction
Eugene L. Asahchop, … , M. John Gill, Christopher Power
Eugene L. Asahchop, … , M. John Gill, Christopher Power
Published December 6, 2018
Citation Information: JCI Insight. 2018;3(23):e122450. https://doi.org/10.1172/jci.insight.122450.
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Research Article AIDS/HIV Neuroscience

HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA–455-3p induction

Abstract

Symptomatic distal sensory polyneuropathy (sDSP) is common and debilitating in people with HIV/AIDS, leading to neuropathic pain, although the condition’s cause is unknown. To investigate biomarkers and associated pathogenic mechanisms for sDSP, we examined plasma miRNA profiles in HIV/AIDS patients with sDSP or without sDSP in 2 independent cohorts together with assessing related pathogenic effects. Several miRNAs were found to be increased in the Discovery Cohort (sDSP, n = 29; non-DSP, n = 40) by array analyses and were increased in patients with sDSP compared with patients without sDSP. miR–455-3p displayed a 12-fold median increase in the sDSP group, which was confirmed by machine learning analyses and verified by reverse transcription PCR. In the Validation Cohort (sDSP n = 16, non-DSP n = 20, healthy controls n = 15), significant upregulation of miR–455-3p was also observed in the sDSP group. Bioinformatics revealed that miR–455-3p targeted multiple host genes implicated in peripheral nerve maintenance, including nerve growth factor (NGF) and related genes. Transfection of cultured human dorsal root ganglia with miR–455-3p showed a concentration-dependent reduction in neuronal β-III tubulin expression. Human neurons transfected with miR–455-3p demonstrated reduced neurite outgrowth and NGF expression that was reversed by anti–miR–455-3p antagomir cotreatment. miR–455-3p represents a potential biomarker for HIV-associated sDSP and might also exert pathogenic effects leading to sDSP.

Authors

Eugene L. Asahchop, William G. Branton, Anand Krishnan, Patricia A. Chen, Dong Yang, Linglong Kong, Douglas W. Zochodne, Bruce J. Brew, M. John Gill, Christopher Power

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Figure 4

Immunofluorescence and immunodetection in hDRGs.

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Immunofluorescence and immunodetection in hDRGs. Cultured hDRGs were tra...
Cultured hDRGs were transfected with (A–C) miRNA-NC, (D–F) miR–455-3p, or (G–I) miR–455-3p and antagomir for 48 hours. After transfection, cells were fixed and immunolabeled with anti–β-III tubulin (green) or anti-NGF (red) or stained with DAPI (blue). Images were captured by confocal microscopy. Immunofluorescence was a single experiment in triplicates or quadruplets. Scale bars 48 μm. (J) For in-cell immunodetection, cultured hDRGs were transfected with miRNA-NC or miR–455-3p at different concentrations for 48 hours. This experiment was repeated 3 times. This shows a representative experiment. (K) Cultured hDRGs were transfected with miRNA-NC, miR–455-3p, or miR–455-3p and antagomir for 48 hours. After transfection, cells were incubated with anti–β-III tubulin antibodies and immunofluorescence was quantified. In-cell analysis experiments were done 3 times and the results merged, averaged, and analyzed using 1-way ANOVA (Kruskal-Wallis) test. *P < 0.05, **P < 0.01. Antag, antagomir.