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Extracell Vesicles Circ Nucleic Acids 2020;1:20-56 I http://dx.doi.org/10.20517/evcna.2020.10 Page 45

33. Effects of marijuana on viral transcription in HIV-1 infected cells and resulting extracellular
vesicle release

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Authors: Catherine De Marino , Maria Cowen , Bianca Cotto , Sara Jane Ward , Ronald Tuma , Prasun
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Datta , Leah H. Rubin , Dianne Langford , Fatah Kashanchi 1
E-mail: mcowen4@gmu.edu
Affiliations:
1 Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA,
USA.
2 Department of Neuroscience, Temple University, Philadelphia, PA, USA.
3 Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
4 Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Abstracts: As of 2016, roughly 18.2 million of the approximately 36.9 million people living with HIV
globally were receiving combination antiretroviral therapy (cART). Despite decades of research and
development of this complex drug regimen, which is effective in the prevention of new infections, cells
with an integrated HIV-1 genome have leaky transcription which can produce viral RNAs and proteins.
These viral products can then be packaged into extracellular vesicles (EVs) and released from the infected
cell. EVs, specifically exosomes, produced from HIV-1 infected cells contain viral mRNAs and incubation
of these exosomes with cells caused a significant increase in the production of the proinflammatory
cytokines, implicating EVs as a possible mechanism for the chronic inflammation observed in the CNS
[1-4]
of people living with HIV-1 on antiretroviral therapy . Previous studies have shown that marijuana use
in people living with HIV is associated with a lower viral load and high CD4+ T-cell count, suggesting a
potential therapeutic application. Here, we investigated the effects of cannabinoids, CBD and THC, on
viral transcription in HIV-1 infected cells and resulting changes in EV release. Our data suggests CBD
and THC can act as viral transcription inhibitors, potentially through two independent mechanisms. Here
we show that treatment of CBD and THC on virally infected myeloids results in lowered production of
intracellular and extracellular viral RNAs, such as short non-coding (TAR) and genomic (env) transcripts,
as well as lowered downstream viral proteins, such as capsid protein (Pr55), cleaved capsid protein (p24)
and accessory protein (Nef). Additionally, the results show a significant reduction in EVs released from
infected cells. These studies are significant in that marijuana may provide a protective effect by alleviating
the pathogenic effects of EVs in HIV-1 and CNS-related infections.

REFERENCES
1. Narayanan A, Iordanskiy S, Das R, et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. J
Biol Chem 2013;288:20014-33.
2. Sampey GC, Saifuddin M, Schwab A, et al. Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines
through trans-activating response (TAR) RNA. J Biol Chem 2016;291:1251-66.
3. Barclay RA, Schwab A, DeMarino C, et al. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem
2017;292:14764.
4. DeMarino C, Pleet ML, Cowen M, et al. Publisher correction: antiretroviral drugs alter the content of extracellular vesicles from HIV-1-
infected cells. Sci Rep 2018;8:14303.

34. Extracellular vesicles release from infected cells prior to virion release

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Authors: Yuriy Kim , Daniel Pinto , Gifty Mensah , Maria Cowen , James Erickson , Renaud Mahieux ,
Fatah Kashanchi 1
E-mail: ykim78@masonlive.gmu.edu