Cannabinoid Regulation of Viral Transcription and Release of Extracellular Vesicles from cART Treated HIV-1-Infected Monocytes

Currently, there is no cure for human immunodeficiency virus type 1 (HIV-1) infection. However, combined antiretroviral therapy (cART) aids in viral latency and prevents the progression of HIV-1 infection into acquired immunodeficiency syndrome (AIDS). cART has extended many lives, but people living with HIV-1 (PLWH) face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) that range from asymptomatic HAND to HIV-1-associated dementia. HAND has been attributed to chronic inflammation and low-level infection within the central nervous system (CNS) caused by proinflammatory cytokines and viral products. These molecules are shuttled into the CNS within extracellular vesicles (EVs), lipid bound nanoparticles and are released from cells as a form of intercellular communication. Here we explore the use of cannabidiol (CBD), as a promising and potential therapeutic for HAND patients, and a similar synthetic molecule, HU308. The data shows that both CBD and HU308 decrease non-coding and coding viral RNA (TAR and env) as well as proinflammatory cytokines as IL-1β and TNF-α mRNA. This decrease in viral RNA occurs in vitro differentiated primary macrophages, in EVs released from HIV-1-infected cells monocytes, infected neurospheres, and in vivo, a humanized mouse model of HIV-1 infection demonstrated a decrease in circulating viral RNA with HU308 treatment. Overall, CBD or HU308 may be a viable option to decrease EV release and associated cytokines which would dampen the virus spread and may be used in effective treatment of HAND in combination with cART.

Author

• Williams, Anastasia

Identifier

hdl:1920/15251

OAI identifier oai:identifier

oai:MARS:1920/15251