# Role of miRNAs in Methamphetamine/HIV-mediated Immune Activation

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $396,250

## Abstract

Abstract
Chronic immune activation is a major factor of HIV disease progression. Bacterial products of microbial translocation
from the gut are likely to be a cause of systemic immune activation in chronic HIV infection. However, the
mechanism(s) responsible for chronic immune activation remain to be determined. Given that drugs of abuse
contribute greatly to HIV infection, it is crucial to study whether use of methamphetamine (METH), one of the most
commonly abused drugs among HIV-infected individuals, is associated with HIV infection-related systemic
inflammation and chronic immune activation. We hypothesize that METH use result in inflammation and immune
activation through induction of the inflammatory and neurotoxic miRNAs, which facilitate HIV replication and
the BBB/CNS injury. We propose three specific aims to address this hypothesis. In Aim 1, we will determine the
plasma levels of several key microbial components and immune activation markers in METH users with or without
HIV infection. We will also measure the plasma levels of inflammatory/neurotoxic miRNAs in these subjects; In Aim
2, we will study whether monocytes and T lymphocytes from METH users express higher levels of the
inflammatory/neurotoxic miRNAs than those from non-METH users. We will also investigate whether METH has
synergetic effect with the microbial products on enhancing HIV infection of macrophages and whether the cells from
METH users are more susceptible to HIV infection than those from control subjects; In Aim 3, we will examine the
effects of METH and/or HIV on the expression of inflammatory and neurotoxic miRNAs in the brain tissues and CSF
from subjects with or without HIV-associated neurocognitive disorder (HAND). In addition, we will mechanistically
investigate the role of inflammatory/neurotoxic miRNAs (let-7, miR-17, -20a, -21, -132, -146a) in the BBB and
neuronal injury. These proposed studies with combinational in vitro (Aim 3), ex vivo (Aim 2), and in vivo (Aims 1, 2,
3) approaches are clinically relevant and significant, and will determine previously unrecognized biomarkers and
mechanisms for METH use-mediated systemic inflammation/immune activation and impairment of the BBB/CNS.

## Key facts

- **NIH application ID:** 9880418
- **Project number:** 5R01DA045568-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** WENZHE HO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880418

## Citation

> US National Institutes of Health, RePORTER application 9880418, Role of miRNAs in Methamphetamine/HIV-mediated Immune Activation (5R01DA045568-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9880418. Licensed CC0.

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