HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1-associated dementia.
Viral and cellular products from HIV-1-infected and/or immune competent mononuclear phagocytes (MP) (brain macrophages and microglia) affect neuronal function during HIV-1-associated dementia (HAD). Neurotoxic MP factors include, but are not limited to, pro-inflammatory cytokines, chemokines, platelet activating factor, arachidonic acid and its metabolites, nitric oxide, progeny virions and viral structural and regulatory proteins. The mechanisms for immune-mediated neural injury in HAD, only now, are being unraveled. In this regard, we reviewed the current knowledge of how postmitotic neurons, which can neither divide nor be replaced, are damaged by MP secretory activities. Linking neuronal function with brain MP activation was made possible by placing viral and/or immune products onto neurons and measuring cell signaling events or through ex vivo electrophysiological tests on MP-treated brain slices. Such linkages are shown, in this report, by select demonstrations of MP factors which cause neuronal dysfunction in HAD.
Xiong
H
H
The Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, NE 68198-5215 USA.
Zeng
Y C
YC
Lewis
T
T
Zheng
J
J
Persidsky
Y
Y
Gendelman
H E
HE
D015526:AIDS Dementia Complex / Q000276:immunology / Q000473:pathology / Q000821:virology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D016923:Cell Death; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D017628:Microglia / Q000378:metabolism* / Q000821:virology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D019707:Receptors, Chemokine / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D018925:Chemokines; D016207:Cytokines; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D019707:Receptors, Chemokine; D054322:tat Gene Products, Human Immunodeficiency Virus