HIV-1 gp120 Interactions with Nicotine Modulate Mitochondrial Network Properties and Amyloid Release in Microglia

Topic: Brain proteins, microglia and lab models

Human immunodeficiency virus (HIV) infections remain a significant public health burden globally with infected individuals at high risk for cognitive decline and memory loss even on combination antiretroviral therapy. Almost half of HIV infected individuals smoke, which drives poorer health outcomes including a higher dementia rate. Microglia are the brain's immune cells that serve as a persistent HIV reservoir contributing to neuroinflammatory signaling. We examined interactions between the HIV envelope glycoprotein gp120 and nicotine within human microglia cells (HMC3) that endogenously express chemokine receptor 5 (CCR5) and nicotinic acetylcholine receptors (nAChRs). Liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI/MS) shows that gp120 alters mitochondria proteins within HMC3 cells. In the presence of nicotine, gp120 increased the expression of mitochondrial prohibitin 2 (PHB2), cytochrome c (cyt c), and mitofusin 2 (MFN2) but decreased fission 1 (FIS1) levels. An analysis of mito-YFP expression confirms that interaction between nicotine and gp120 increases the size and branching of mitochondrial networks. Interaction between nicotine and gp120 is also surprisingly found to promote the release of amyloid precursor protein (APP) peptides from microglia. This was accompanied by visualization of amyloid containing vesicles that colocalized with the autophagy protein LC3B-II in the cell. Taken together, our findings show that interaction between nicotine and gp120 impact microglia in a manner that regulates mitochondrial proteins and network properties and impacts amyloid protein management and release within microglia. These mechanisms may contribute to understanding neuroinflammatory signaling in smokers with HIV.

Key findings

• Human immunodeficiency virus (HIV) infections remain a significant public health burden globally with infected individuals at high risk for cognitive decline and memory loss even on combination antiretroviral therapy.
• Taken together, our findings show that interaction between nicotine and gp120 impact microglia in a manner that regulates mitochondrial proteins and network properties and impacts amyloid protein management and release within microglia.

Why it matters

In human microglia cells in the laboratory, interaction between HIV gp120 and nicotine altered mitochondrial proteins and network properties and promoted release of amyloid precursor protein peptides. This is early cell research on HIV-related cognitive risk and does not show a treatment or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1007/s11064-025-04357-3
• PubMed: 39992414
• Original source →
• Free full text: Neurochemical Research →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{graur2025-39992414,
  author  = {Graur, Alexandru and Erickson, Natalie and Sinclair, Patricia and Nusir, Aya and Kabbani, Nadine},
  title   = {{HIV-1 gp120 Interactions with Nicotine Modulate Mitochondrial Network Properties and Amyloid Release in Microglia}},
  journal = {Neurochemical Research},
  year    = {2025},
  doi     = {10.1007/s11064-025-04357-3},
  pmid    = {39992414},
  url     = {https://doi.org/10.1007/s11064-025-04357-3}
}

Studies this one cites

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• Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome Autophagy · 2014-07-22 · usefulness score 46/100 · Inflammation and the immune system

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