HIV-1 infection in the brain results in neurodegeneration.

(A) Effects of HIV-1 on target cells in the CNS. Microglia and macrophages infected with HIV-1 and/or exposed to viral proteins (such as Tat and gp120) along with infected astrocytes secrete a mix of host and viral factors. This induces a toxic and inflammatory environment that contributes to the complex process of neuronal dysfunction and death in infected individuals that develop HAND. (B) HIV-1 Gag counteracts an innate restriction imposed by APP resulting in overproduction of neurotoxic Aβ. APP traps HIV-1 Gag polyprotein in cell membrane regions enriched in secretases during late-stage viral assembly and/or production in microglia or macrophages. To counteract this, Gag promotes secretase-dependent APP processing resulting in overproduction of toxic Aβ isoforms. Aβ, β-amyloid; APP, amyloid precursor protein; CNS, central nervous system; Gag, group-specific antigen; gp120, envelope glycoprotein 120; HAND, HIV-1 associated neurocognitive disorders; HIV-1, human immunodeficiency virus type 1; Tat, transactivator of transcription.