Identification of EcoHIV-Infected Cells in Microglia-Manipulated Transgenic Mice

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Combined antiretroviral therapy (cART) has improved life for people living with HIV (PLWH), but many still develop HIV-associated neurocognitive disorders (HAND).
• Understanding how HIV affects the central nervous system requires a reliable HIV model.
• Previous studies utilized a chimeric HIV (EcoHIV) model in rats to study neurocognitive impairments, but EcoHIV's cell-type distribution in the brain remained unclear.

Purpose of the Study:

• To determine if microglia are the main cell type responsible for HIV expression and reservoirs in the brain.
• To investigate the neuroanatomical distribution of EcoHIV in a mouse model.
• To establish a model for studying microglial alterations in HIV neurological disease.

Main Methods:

• EcoHIV was modified with mScarlet fluorescence and injected into Tmem119-EGFP knock-in mice, which express EGFP in microglia.
• In vitro studies assessed EcoHIV localization in primary rodent brain cells.
• In vivo studies analyzed the co-localization of mScarlet (HIV) and EGFP (microglia) signals in the mouse brain.

Main Results:

• In vitro, EcoHIV-mScarlet primarily localized to microglia-like cells.
• In vivo, EcoHIV-mScarlet injection led to significant HIV expression in the mouse brain.
• Co-localization of mScarlet and EGFP signals confirmed microglia as the main cell type harboring HIV.

Conclusions:

• Microglia are the predominant cell type harboring HIV in the brain.
• The EcoHIV rodent model is valuable for studying microglial changes and HIV reservoirs in the brain.
• This model can advance research into the neurological mechanisms of HAND.