Methamphetamine increases HIV infectivity in neural progenitor cells.

Area of Science:

• Neuroscience
• Virology
• Toxicology

Background:

• HIV-1 infection and methamphetamine (METH) abuse often co-occur, potentially leading to synergistic pathological effects.
• HIV-positive METH users exhibit higher viral loads and neurological complications, but METH's direct impact on HIV infection and neurocognition remains unclear.

Purpose of the Study:

• To investigate how METH affects HIV infection in neural progenitor cells (NPCs).
• To elucidate the molecular mechanisms, specifically the role of NFκB/SP1-mediated HIV LTR activation.
• To assess METH's impact on NPC differentiation and neurogenesis in the context of HIV infection.

Main Methods:

• Infection of mouse and human NPCs with EcoHIV and HIV, respectively, with or without METH exposure.
• Transfection of cells with HIV LTR promoter variants followed by METH treatment.
• Assessment of HIV production, LTR transcriptional activity, and NPC neuronal differentiation in vitro and in vivo.

Main Results:

• Pretreatment with METH significantly increased HIV production in both mouse and human NPCs.
• METH treatment induced HIV LTR promoter activity, dependent on NFκB and SP1 signaling.
• METH pretreatment reduced neuronal differentiation of HIV-infected NPCs, with daughter cells showing latent HIV infection.

Conclusions:

• METH enhances HIV infectivity in NPCs via NFκB/SP1-dependent HIV LTR activation.
• METH alters NPC neurogenesis, potentially contributing to neurocognitive deficits in HIV-infected individuals.
• These findings highlight a mechanism linking METH abuse to exacerbated neurological issues in HIV patients.