TY - JOUR
T1 - HIV-1-associated dementia
T2 - A metabolic encephalopathy perpetrated by virus-infected and immune-competent mononuclear phagocytes
AU - Anderson, Eric
AU - Zink, Walter
AU - Xiong, Huangui
AU - Gendelman, Howard E.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Infection of the nervous system by HIV-1 commonly causes a broad range of cognitive, behavioral, and motor abnormalities called, in its most severe form, HIV-1-associated dementia (HAD). HAD is a metabolic encephalopathy caused by productive viral infection of brain mononuclear phagocytes (MPs) (perivascular and parenchymal brain macrophages and microglia) and sustained by paracrine-amplified, inflammatory, neurotoxic responses. MP neurotoxins are, in large measure, homeostatic secretory products that can have a negative effect on neuronal cell function when produced in abundance. Proinflammatory cytokines, chemokines, platelet-activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinic acid, progeny virions, and viral structural and regulatory proteins are all included as part of these cellular and viral toxic elements. In addition, neuronal damage can occur directly by engaging specific receptors or through inducing widespread inflammatory activities in brain tissue that ultimately induce neuronal demise. The mechanisms for immune- and viral-mediated neural injury in HAD are made more striking by the effects of abused drugs on cognitive function, Ultimately, linkages between neuronal function and disordered MP immunity will provide insights into how HIV-1 infection of the brain leads to compromised mental function as well as providing clues into the pathogenesis of other neurodegenerative disorders.
AB - Infection of the nervous system by HIV-1 commonly causes a broad range of cognitive, behavioral, and motor abnormalities called, in its most severe form, HIV-1-associated dementia (HAD). HAD is a metabolic encephalopathy caused by productive viral infection of brain mononuclear phagocytes (MPs) (perivascular and parenchymal brain macrophages and microglia) and sustained by paracrine-amplified, inflammatory, neurotoxic responses. MP neurotoxins are, in large measure, homeostatic secretory products that can have a negative effect on neuronal cell function when produced in abundance. Proinflammatory cytokines, chemokines, platelet-activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinic acid, progeny virions, and viral structural and regulatory proteins are all included as part of these cellular and viral toxic elements. In addition, neuronal damage can occur directly by engaging specific receptors or through inducing widespread inflammatory activities in brain tissue that ultimately induce neuronal demise. The mechanisms for immune- and viral-mediated neural injury in HAD are made more striking by the effects of abused drugs on cognitive function, Ultimately, linkages between neuronal function and disordered MP immunity will provide insights into how HIV-1 infection of the brain leads to compromised mental function as well as providing clues into the pathogenesis of other neurodegenerative disorders.
KW - Chemokines
KW - HIV-1
KW - HIV-1 encephalitis
KW - HIV-1-associated dementia
KW - Neurotoxicity
KW - Proinflammatory cytokines
KW - Viral structural and regulatory proteins
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U2 - 10.1097/00126334-200210012-00004
DO - 10.1097/00126334-200210012-00004
M3 - Article
C2 - 12394782
AN - SCOPUS:0036800457
SN - 1525-4135
VL - 31
SP - S43-S54
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - SUPPL. 2
ER -