CBD Regulation of Extracellular Vesicles, and their Cargo Released from HIV-1 Infected Cells

Human immunodeficiency virus -1 (HIV-1) is an infection that impacts 38 million people globally. HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS) and although there is no cure for HIV infection, people living with HIV (PLWH) are treated with combined antiretroviral therapy (cART), that provides viral latency and prevents the progression into AIDS. Even with cART treatment, PLWH face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) which encompasses a variety of CNS disorders ranging from asymptomatic to early onset Alzheimer’s disease. HAND is attributed to the chronic inflammation seen in the central nervous system of PLWH. One problem with treating this inflammation is the blood-brain barrier (BBB) which makes it hard for drugs to reach the brain. Cannabidiol (CBD), is a promising therapeutic molecule for HAND patients as it has been shown to reduce inflammation in other diseases such as rheumatoid arthritis and can freely cross the BBB. Furthermore, our lab has shown CBD treatment reduces viral RNA packaged in extracellular vesicles (EVs) released from HIV-1 infected cells. Previous studies have shown viral RNA encapsulated by EVs incite the production of proinflammatory cytokines in neighboring cells. Thus, CBD may reduce inflammation caused by EV encapsulated viral RNA. This study attempts to further understand this phenomenon by identifying the impacts of CBD on isolated EV subpopulations released from HIV-1 infected monocytes. To do this EV subpopulations were isolated by density using ultracentrifugation to create 5 populations (2K, 10K, 100K, 167K (4 h), 167K (16h)). The data shows that CBD impacts EV release and cargo of different populations in unique ways. For example, there was an overall increase in EV concentration, proinflammatory cytokine RNA, and viral RNA released in the 10K population. But, the 100K population had significant decrease in EV concentration as well as proinflammatory cytokine and viral RNA. The difference in EV populations may be due to CBD’s ability to induce autophagy, and/or through its interaction with cytoplasmic proteins that take part in EV biogenesis. Overall, this indicates the need to further understand the affect CBD has on EV biogenesis in HIV-1 infected cells.