HIV-1 and opiates modulate miRNA profiles in extracellular vesicles.

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Opiate abuse heightens HIV transmission risk and worsens HIV neuropathology through inflammation and altered immune function.
• Exosomal EVs (xEVs) carry microRNAs (miRNAs) that may change with HIV infection or opiate use.
• Understanding these miRNA changes is crucial for addressing co-occurring HIV and opiate use disorders.

Purpose of the Study:

• To develop a preliminary exosomal-miRNA biomarker profile in HIV-infected PBMCs under opiate exposure.
• To investigate the effects of these exosome-miRNAs on neuronal function.
• To identify potential mechanisms and therapeutic targets for HIV neuropathology in the context of opiate use.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) infected with HIV were treated with morphine.
• Exosomes were isolated from cell culture supernatants using differential centrifugation.
• Exosomal miRNA expression was analyzed using Nanostring arrays, and effects on neuronal cells (SH-SY5Y) were assessed via calcium signaling and viability assays.

Main Results:

• HIV-1 infection and morphine exposure altered miRNA profiles in PBMC-derived EVs.
• hsa-miR-1246 showed a 12-fold upregulation with morphine exposure.
• Exosomes from HIV-infected PBMCs decreased neuronal viability and calcium signaling, while those from ART-treated PBMCs increased viability.

Conclusions:

• HIV-1 and morphine induce differential miRNA expression in PBMC-derived exosomes.
• These findings suggest potential synergistic effects impacting viral replication and neuronal function.
• The identified miRNA changes may represent novel therapeutic targets for HIV neuropathology and opiate use disorder.