Figures & data
Figure 1 The complex feedback and feedforward relations of neuroendocrine immune mediators in regulating the central nervous system and peripheral immune responses to HIV infection.
Notes: Disruption of homeostatic mechanisms by infection is evident at multiple control points in stress and immune system regulation. HIV infection has direct and indirect effects on non-hypothalamic CRH and the hypothalamic–pituitary–adrenal axis to disrupt immune defenses.
Abbreviations: ACTH, adrenocorticotropin; CRH, corticotropin-releasing hormone; IL, interleukin; IFN-γ, interferon gamma; ROS, reactive oxygen species; TAT, transactivator of transcription; TNF-α, tumor necrosis factor-alpha.
Figure 2 Some of the complex interactions of HIV infection in the central nervous system.
Notes: HIV infection triggers chronic stress hormone release; elevated levels of cortisol can trigger glucocorticoid resistance in susceptible immune cells and tissues. This engenders a proinflammatory environment, which generates a feedforward cascade of neuroinflammation. Inflammatory stimuli from virions, viral proteins gp120 and TAT, increased glutamate, cytokines/chemokines, free radicals, and membrane destabilization agents all contribute to neurodegeneration. This culminates in locoregional neuronal dysfunction on a microscale, which eventually translates to both structural and functional deficits leading to clinical neurologic and cognitive impairment.
Abbreviations: ACTH, adrenocorticotropin; CRH, corticotropin-releasing hormone; SNS, sympathetic nervous system; TAT, transactivator of transcription.
Figure S1 HIV infection in the central nervous system involves both HIV-infected and noninfected neuronal support cells.
Notes: Macrophages, monocytes, and glial elements modulate actions of neurons through astrocytes. Virions and viral protein components (gp120, TAT), cytokines, membrane destabilization molecules, and glutamate (with other agents) stimulate remaining glial and other immune cells/tissues, generating a proinflammatory neurotoxic state. These adversely affect astrocytes, diminishing their support of neurons. This promotes neuronal dysfunction with loss of synaptic integrity and plasticity, morphologic and functional impairment, and apoptosis. Continued HIV invasion and replication perpetuate a cascading cycle of increasing inflammation and neurodegeneration. Macroscopic structural deficits develop with loss of cortical and subcortical functions and neuronal connectivity leading to clinical sequelae.
Abbreviation: TAT, transactivator of transcription.
