# Nicotine and NLRP3 Inflammasome in HIV-1-Associated CNS Inflammation

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $758,730

## Abstract

PROJECT SUMMARY
Human immunodeficiency virus type 1 (HIV-1) infection remains incurable, with over 38 million people affected
worldwide. While HIV-1 is known to enter the brain within the first two weeks of infection, it is estimated that 20-
50% of people with HIV-1 will develop HIV-associated neurocognitive disorder (HAND). Neuroinflammation is
thought to play a key role in HIV-1 persistence, and substance use disorders, including smoking, may further
contribute to inflammation and cognitive decline. In this study, we aim to investigate the impact of nicotine, a key
component of tobacco smoking, on NLRP3 inflammasome activation in the central nervous system of people
with HIV-1 and substance use disorders. Our research addresses a critical gap in understanding how
inflammation contributes to HIV-1 persistence and cognitive decline in smokers with HIV-1. We will investigate
how HIV-1 infection and nicotine exposure interact to activate the inflammasome and increase inflammation in
human tonsil explants and iPSC-derived microglia to achieve our goals. We will use a newly developed xenograft
humanized mouse model to track inflammasome differential expression and activation in brain regions,
specifically in latent and productively infected and bystander cells. Finally, we will analyze post-mortem brain
samples from individuals with HIV-1 and compare the expression of markers associated with NLRP3
inflammasome activation in smokers versus non-smokers. The proposed research will provide crucial insights
into the mechanisms underlying neuroinflammation and cognitive decline in people with HIV-1 and substance
use disorders. Our work will elucidate the role of NLRP3 inflammasome activation in HIV-1-associated
inflammation and identify potential therapeutic targets to address this issue. By advancing our understanding of
inflammation and the immune response to HIV-1 in smokers, we hope to develop novel treatments for this
population's cognitive decline and immune dysregulation.

## Key facts

- **NIH application ID:** 10811398
- **Project number:** 1R01DA059876-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Schahram Akbarian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $758,730
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811398

## Citation

> US National Institutes of Health, RePORTER application 10811398, Nicotine and NLRP3 Inflammasome in HIV-1-Associated CNS Inflammation (1R01DA059876-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10811398. Licensed CC0.

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