Document 0524
 DOCN  M9490524
 TI    HIV-1 infection of the developing nervous system: central role of
       astrocytes in pathogenesis.
 DT    9411
 AU    Blumberg BM; Gelbard HA; Epstein LG; Department of Neurology, University
       of Rochester, NY 14642.
 SO    Virus Res. 1994 May;32(2):253-67. Unique Identifier : AIDSLINE
       MED/94346056
 AB    Recent studies in our laboratory and that of Dr. Howard Gendelman have
       revealed two important pathways for neuronal damage during HIV-1
       encephalopathy in children. First, substantial numbers of astrocytes are
       actively or latently infected with HIV-1. Astrocyte infection may lead
       to neuronal dysfunction through loss of supporting growth factors,
       excitotoxicity due to dysregulation of neurotransmitter reuptake, and
       loosening of the blood-brain barrier permitting further seeding of HIV-1
       in the CNS. Significantly, infection of astrocytes is marked by
       near-exclusive synthesis of early regulatory gene products of HIV-1,
       while structural proteins characteristic of productive infection are
       found in macrophages, microglia and multinucleated giant cells. We
       propose the term 'restricted' to denote the non-productive infection
       found in astrocytes. Second, HIV-1-infected macrophages initiate
       inflammatory processes which are amplified through cell-cell
       interactions with astrocytes. Macrophage-astrocyte interactions produce
       arachidonic metabolites and potentially neurotoxic cytokines (TNF-alpha
       and IL-1 beta), leading to astroglial activation and proliferation which
       then amplifies these cellular processes. These new findings suggest that
       two major pathways leading to neurotoxicity in pediatric AIDS
       encephalopathy are linked to HIV-1 infection through astrocyte-mediated
       processes, and help explain how small numbers of productivity infected
       cells indirectly cause widespread tissue pathology and elicit profound
       neurological impairment.
 DE    Astrocytes/MICROBIOLOGY/PATHOLOGY/*PHYSIOLOGY  AIDS Dementia
       Complex/*ETIOLOGY/MICROBIOLOGY/PATHOLOGY  Cell Communication  Cell Death
       Child  Human  *HIV-1/PHYSIOLOGY/PATHOGENICITY
       Macrophages/MICROBIOLOGY/PHYSIOLOGY  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  JOURNAL ARTICLE  REVIEW  REVIEW, ACADEMIC

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).