Development of a Human-Mouse Chimera to Study the Toxic Effects of HIV Antiretroviral Drugs
Session Number
Project ID: MEDH 19
Advisor(s)
Dr. Jennillee Wallace, RUSH University
Discipline
Medical and Health Sciences
Start Date
17-4-2024 8:15 AM
End Date
17-4-2024 8:30 AM
Abstract
The course of treatments for HIV has been revolutionized by the development of antiretroviral drugs. However, in many instances, these drugs induce toxicity via mitochondrial dysfunction and the release of neurotoxins, and long-term toxicity remains an area of worry for people living with HIV. Our objective is to develop a humanized mouse model to study the toxic effects of HIV antiretroviral drugs on tissue monocyte-derived macrophages. First, immune-compromised mice were engrafted with human immune cells and we then verified whether these cells migrated to different tissues. To assess human cell trafficking to tissues, DNA was isolated from the brain, lungs, liver, heart, kidney, and spleen. We performed qRT-PCR using human and mouse- specific primers to determine the human: mouse DNA ratio, and quantify human DNA in the mouse tissues. Ongoing and future studies will utilize this model to further assess the toxic effects on monocyte- derived myeloid cells and their subsequent impact on brain tissue.
Development of a Human-Mouse Chimera to Study the Toxic Effects of HIV Antiretroviral Drugs
The course of treatments for HIV has been revolutionized by the development of antiretroviral drugs. However, in many instances, these drugs induce toxicity via mitochondrial dysfunction and the release of neurotoxins, and long-term toxicity remains an area of worry for people living with HIV. Our objective is to develop a humanized mouse model to study the toxic effects of HIV antiretroviral drugs on tissue monocyte-derived macrophages. First, immune-compromised mice were engrafted with human immune cells and we then verified whether these cells migrated to different tissues. To assess human cell trafficking to tissues, DNA was isolated from the brain, lungs, liver, heart, kidney, and spleen. We performed qRT-PCR using human and mouse- specific primers to determine the human: mouse DNA ratio, and quantify human DNA in the mouse tissues. Ongoing and future studies will utilize this model to further assess the toxic effects on monocyte- derived myeloid cells and their subsequent impact on brain tissue.