Microglia, HIV and drugs of abuse

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

We are examining how rodent microglia respond to psychostimulants such as methamphetamine in both a chronic and acute exposure model. Ongoing work has identified dosing of methamphetamine that causes unique activation of microglia in the striatum that can be used to examine how activated microglia can affect the surround neurons. We have developed a novel microglial cell line that has a modified HIV provirus inserted into the genome. This provirus lacks the gag and pol genes but expresses a luciferase which can be used to monitor effectors of proviral transcriptional activity. We have used CRISPR to target the long terminal repeat (LTR) promoter of HIV in this cell line and are using it to evaluate CRISPR-based approaches to alter HIV proviral activity in microglia. Microglia are notoriously difficult to target with transgenic material. We are have recently identified an AAV vector capable of delivering transgenic material (DNA, RNA, CRISPR ribonucleoproteins) to microglia. Based on this AAV platform, we are developing vectors capable of expressing in microglia. These tools will allow us to more readily examine the effect of microglia production of HIV proteins and the effects on surrounding cells such as neurons when exposed to substances of addiction. Lastly, we have begun investing EcoHIV, a modified HIV to infect only rodent cells, as a model to study the interactions of microglia, HIV and substances of addiction.