Neural progenitors and HIV-1-associated central nervous system disease in adults and children.
The human immunodeficiency virus type 1 (HIV-1) is a neurotrophic lentivirus that enters and infects the central nervous system (CNS) of adults and children, giving rise to the clinical syndromes of AIDS-dementia complex (ADC) in adults and HIV-1-associated progressive encephalopathy (PE) in pediatric patients. The clinical presentation and progression of neuroAIDS in the developing brain of children is distinct from that seen in adult patients. Neuroimaging, and upon autopsy, neuropathological findings corresponding to clinical disease in pediatric patients include impaired brain growth, reactive gliosis, myelin pallor, calcifications of the basal ganglia, cortical and cerebral atrophy with neuronal loss and ventricular enlargement, and abnormalities of cerebral vasculature. Although there is some overlap with neuropathologic findings in adult patients, ADC in adults is more typically a late development, often complicated by opportunistic infections of the CNS. The neuropathogenesis of ADC and PE is incompletely understood. One population of CNS cells critical for brain development and response to injury and inflammation are neural progenitors cells, and it has therefore been suggested that these cells may be involved in the neuropathogenesis of ADC, and especially PE. This review examines the neurobiology of neural progenitor cells and the possibility that HIV-1 infection of neural progenitors, exposure of neural progenitors to virus, viral products, or progenitor exposure to HIV-1 associated neuroinflammatory substances and neurotoxins might contribute to the neuropathogenesis of AIDS in adults and children. That some of the clinical differences between ADC and PE might, in part, be explained by differences in neural progenitor involvement will also be considered.
Schwartz
Lynnae
L
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. schwartl@ninds.nih.gov
Major
Eugene O
EO
D015526:AIDS Dementia Complex / Q000209:etiology*; D000328:Adult; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D002648:Child; D015497:HIV-1; D006801:Humans; D009474:Neurons / Q000502:physiology / Q000821:virology*; D019718:Receptors, CXCR4 / Q000502:physiology; D013234:Stem Cells / Q000502:physiology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha