# Effect of Methamphetamine and/or HIV on Human iPSCs-derived microglia and Neuron

> **NIH NIH R21** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $237,750

## Abstract

Abstract
 METH, a potent addictive psychostimulant, is one of the most commonly abused drugs in the United States.
METH abuse is highly prevalent in HIV-infected individuals, which presents unique challenges for HIV
prevention and treatment. Given the overlap impact of METH use and HIV on neuronal damage in the CNS, it
becomes urgent to understand the role of interplays between METH and HIV in the pathogenesis of HIV-
associated neurocognitive disorders (HAND). However, studies of HAND have been hampered by difficulties in
collecting primary microglial and neuronal cells from autopsy or biopsy of HIV patients. Recent success in
generating microglia and neurons from human induced pluripotent stem cell lines (iPSCs) now offers a great
opportunity to study the direct interactions between HIV-infected microglia and neurons. The proposed studies
will use iPSC-derived microglia (iPSC-MG) and neuron (iPSC-N) to examine our overall hypothesis that METH
and/or HIV inhibit the intracellular HIV restriction factors and induce the inflammasomes and neurotoxic
miRNAs in iPSC-MG, which facilitate HIV infection/replication in iPSC-MG and promote the death of iPSC-N.
We propose two specific aims to address this hypothesis:
 Aim 1 To determine whether METH enhances HIV infection/replication in iPSC-MG. Mechanistically, we will
examine whether METH and/or HIV inhibit the intracellular HIV restriction factors in iPSC-MG;
 Aim 2 To determine whether METH and/or HIV infection induce expression of the inflammasomes and
neurotoxic miRNAs in iPSC-MG and promote the death of IPSC-N.
This project fits well to the NIDA’s recent interests in studying the impact of drug abuse and/or HIV on human
iPSC-derived CNS cells. The information resulting from the proposed studies using the iPSC-MG and iPSC-N
will provide important insights on how the interplays of two major pathologic factors (HIV and METH) in the
CNS compromise the intracellular anti-HIV immunity of microglia and induce neuronal death, which are the key
mechanisms for HIV infection/persistence in the brain and development of HAND.

## Key facts

- **NIH application ID:** 10031319
- **Project number:** 1R21DA051396-01
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** WENZHE HO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,750
- **Award type:** 1
- **Project period:** 2020-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10031319

## Citation

> US National Institutes of Health, RePORTER application 10031319, Effect of Methamphetamine and/or HIV on Human iPSCs-derived microglia and Neuron (1R21DA051396-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10031319. Licensed CC0.

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