Expression profiling suggests microglial impairment in human immunodeficiency virus neuropathogenesis

Area of Science:

• Neuroimmunology
• Neurovirology
• Molecular Neuroscience

Background:

• Human immunodeficiency virus (HIV) encephalitis (HIVE) is linked to severe neurocognitive impairment.
• Microglia and macrophages expressing CD16 and CD163 are found in HIVE brains.
• Parenchymal microglia in HIV-positive individuals without encephalitis also show altered markers, even without detectable virus.

Purpose of the Study:

• To investigate gene expression profiles of parenchymal microglia in HIV infection.
• To compare microglia from patients with HIVE, HIV with no encephalitis (HIV/noE), and HIV-negative controls.
• To understand microglial activation and its role in HIV-associated neurocognitive disorders.

Main Methods:

• Single-population microarray analysis of laser capture microdissected microglia/macrophages (CD163+, CD16+, CD68+).
• Utilized terminal continuation RNA amplification and a custom array platform.
• Analyzed archival brain tissue from HIVE, HIV/noE, and HIV-negative subjects.

Main Results:

• Microglial transcripts related to cell stress, immune activation, and apoptosis were altered in HIVE and HIV/noE compared to controls.
• Neurotrophic factors were reduced in HIV-infected brains, suggesting a role in neuropathogenesis.
• Transcriptional changes in HIVE were generally more pronounced than in HIV/noE.

Conclusions:

• Microglia play a role in maintaining brain homeostasis, and their dysfunction in chronic inflammation contributes to neuropathogenesis.
• Profiling microglia reveals alterations in pathways and genes relevant to brain diseases.
• Identifying specific molecular targets in microglia may lead to new therapeutic strategies for neurological conditions associated with HIV.