# Cannabinoid modulation of EV composition and function in HIV/SIV infection

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $787,400

## Abstract

Abstract
Extracellular vesicles (EVs) are cargo carrying, quasi-nanovesicles that mediate intercellular communication.
EVs are released by many cell types and are present in body fluids. The composition and function of EVs mirror
that of the producing environment. Thus, EVs are implicated in regulating microbial pathogenesis, extracellular
matrix reorganization, epithelial barrier dysfunction, and inflammatory cell recruitment. Indeed, we and others
have shown that exosomes from body fluids, such as vaginal fluid and semen possess anti-HIV activity, and that
use of drugs of abuse reprograms exosome phenotype and function. The goal of this multi-PI proposal is to
leverage our expertise and resources to evaluate how cannabinoid (delta-9-tetrahydrocannabinol, THC)
modulates the composition and function of EVs during HIV/SIV infection, focusing on the gastrointestinal tract
(GI) and peripheral lymph nodes using the SIV-rhesus macaque model. HIV-infected (HIV+) patients are often
comorbid with drug abuse and cannabis (marijuana) is one of the most commonly used drugs of abuse in the
setting of HIV comorbidity. Approximately, 15–40% of HIV/AIDS patients use cannabis to treat disease
symptoms and ameliorate side effects due to combinatorial antiretroviral therapy (cART). Recent research
findings indicate that administration of THC―the most psychoactive anti-inflammatory cannabinoid in cannabis
is linked to beneficial reduction in systemic inflammation and immune activation in cART-treated HIV+ patients.
In the SIV/macaque model, THC ameliorated SIV disease progression, reduced intestinal T cell
activation/exhaustion and prevented lymph node fibrosis. The benefits of THC is systemic―affecting many
organs, including the GI and lymphoid systems. Gap in knowledge - The underlying mechanisms of THC-
mediated reduction in systemic inflammation, immune activation, and lymph node fibrosis in HIV/SIV infection is
unclear. Since 30 U.S. states allow the use of cannabinoids for medical purposes, with citations of HIV/AIDS as
a condition amenable to such treatment; it is important to understand how THC regulates inflammation and
disease progression in this population. Our preliminary data show that SIV infection results in a time-dependent
increase in the release of proinflammatory EVs (VEH/SIV EV) that promote expression of inflammatory markers
and cytoskeletal remodeling in monocytes and T cells. In contrast, chronic treatment with THC results in secretion
of THC/SIV-EV that are lower in number, carry anti-inflammatory molecules, and counteracts VEH/SIV EV-
induced cytoskeletal remodeling. Based on our published studies and these pilot data, our overarching
hypotheses are that SIV infection of rhesus macaques (RMs) results in the shedding of VEH/SIV EV containing
pro-inflammatory and pro-fibrogenic factors that promote chronic inflammation, epithelial barrier dysfunction,
microbial translocation, and lymphoid fibrosis. Furthermore, chronic THC treatment in the se...

## Key facts

- **NIH application ID:** 10020177
- **Project number:** 5R01DA050169-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Mahesh Mohan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $787,400
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020177

## Citation

> US National Institutes of Health, RePORTER application 10020177, Cannabinoid modulation of EV composition and function in HIV/SIV infection (5R01DA050169-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10020177. Licensed CC0.

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