       Document 0525
 DOCN  M9640525
 TI    Abundant expression of HIV Nef and Rev proteins in brain astrocytes in
       vivo is associated with dementia.
 DT    9604
 AU    Ranki A; Nyberg M; Ovod V; Haltia M; Elovaara I; Raininko R; Haapasalo
       H; Krohn K; Department of Dermatology and Venereal Diseases, University
       of; Helsinki, Finland.
 SO    AIDS. 1995 Sep;9(9):1001-8. Unique Identifier : AIDSLINE MED/96085714
 AB    OBJECTIVE: To relate the expression of HIV regulatory proteins and
       HIV-specific mRNA in the brain cells of infected individuals with
       clinical neurological disease. DESIGN: Formalin-fixed postmortem brain
       tissue from 14 HIV-infected adult patients, with previous repeated
       neurological and neuroradiological examinations, was studied by
       immunohistochemical and molecular biological methods. Samples from
       non-infected brains served as controls. METHODS: Immunohistochemistry
       with monoclonal antibodies (MAb) was combined with in situ RNA
       hybridization. Target cells were identified with MAb to glial fibrillary
       acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and
       Ricinus communis agglutinin (RCA-1; microglia, endothelial cells). For
       HIV, a panel of MAb against HIV Nef, Tat, Rev and Env proteins or probes
       specific for all classes of mRNA (nef), for singly or non-spliced mRNA
       (env) and for non-spliced mRNA (gag/pol) were used. RESULTS: Nef protein
       was detected in subcortical or subpial astrocytes in seven out of 14
       samples, and in multinucleated giant cells in two cases. Gag/pol or env
       mRNA-expressing astrocytes were detected in four cases. In four out of
       five cases studied, HIV Rev, but not Tat, was also expressed in
       astrocytes. Six out of the seven patients with Nef-positive astrocytes
       had suffered from moderate to severe dementia. The patient with most
       rapidly progressing severe dementia showed extensive HIV mRNA expression
       together with Nef and Rev expression in astrocytes. CONCLUSION: In adult
       human brain, astrocytes are infected by HIV and preferentially express
       HIV Nef and Rev proteins but are also sometimes productively infected.
       Astrocyte infection is associated with moderate to severe dementia which
       agrees with recent knowledge on the housekeeping activities of
       astrocytes and their eventual role in learning and memory.
 DE    Adult  Astrocytes/PATHOLOGY/*VIROLOGY  AIDS Dementia
       Complex/PATHOLOGY/*VIROLOGY  Brain/PATHOLOGY/*VIROLOGY  Female  Gene
       Expression Regulation, Viral  Gene Products, nef/*GENETICS  Gene
       Products, rev/*GENETICS  Human  HIV/*GENETICS  Immunoenzyme Techniques
       Male  RNA, Messenger/GENETICS  Support, Non-U.S. Gov't  JOURNAL ARTICLE

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

