Cannabinoids Reduce Extracellular Vesicle Release from HIV-1 Infected Myeloid Cells and Inhibit Viral Transcription

Abstract: Of the 37.9 million individuals infected with human immunodeficiency virus type 1
(HIV-1), approximately 50% exhibit HIV-associated neurocognitive disorders (HAND). We and
others previously showed that HIV-1 viral RNAs, such as trans-activating response (TAR) RNA, are
incorporated into extracellular vesicles (EVs) and elicit an inflammatory response in recipient naïve
cells. Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), the primary cannabinoids present in
cannabis, are effective in reducing inflammation. Studies show that cannabis use in people living with
HIV-1 is associated with lower viral load, lower circulating CD16+ monocytes and high CD4+ T-cell
counts, suggesting a potentially therapeutic application. Here, HIV-1 infected U1 monocytes and
primary macrophages were used to assess the effects of CBD. Post-CBD treatment, EV concentrations
were analyzed using nanoparticle tracking analysis. Changes in intracellular and EV-associated viral
RNA were quantified using RT-qPCR, and changes in viral proteins, EV markers, and autophagy
proteins were assessed by Western blot. Our data suggest that CBD significantly reduces the number
of EVs released from infected cells and that this may be mediated by reducing viral transcription and
autophagy activation. Therefore, CBD may exert a protective effect by alleviating the pathogenic
effects of EVs in HIV-1 and CNS-related infections.