       Document 0371
 DOCN  M9610371
 TI    Human immunodeficiency virus 1 envelope proteins induce interleukin 1,
       tumor necrosis factor alpha, and nitric oxide in glial cultures derived
       from fetal, neonatal, and adult human brain.
 DT    9601
 AU    Koka P; He K; Zack JA; Kitchen S; Peacock W; Fried I; Tran T; Yashar SS;
       Merrill JE; Department of Neurology, University of California, School
       of; Medicine, Los Angeles 90024, USA.
 SO    J Exp Med. 1995 Oct 1;182(4):941-51. Unique Identifier : AIDSLINE
       MED/96018794
 AB    Although microglia are the only cells found to be productively infected
       in the central nervous system of acquired immunodeficiency disease
       syndrome (AIDS) patients, there is extensive white and gray matter
       disease nonetheless. This neuropathogenesis is believed to be due to
       indirect mechanisms other than infection with human immunodeficiency
       virus 1 (HIV-1). Cytokines and toxic small molecules have been
       implicated in the clinical and histopathological findings in CNS AIDS.
       Previously, we have demonstrated in rodent glial cultures the presence
       of biologically active epitopes of gp120 and gp41 that are capable of
       inducing interleukin 1 and tumor necrosis factor alpha. In this study,
       we map the HIV-1 envelope epitopes that induce nitric oxide, inducible
       nitric oxide synthase, interleukin 1, and tumor necrosis factor alpha in
       human glial cultures. Epitopes in the carboxy terminus of gp120 and the
       amino terminus of gp41 induce these proinflammatory entities. In
       addition, we compare HIV-1 infection and pathology in glial cells
       derived from human brain taken at different states of maturation (fetal,
       neonatal, and adult brain) in an effort to address some of the clinical
       and histological differences seen in vivo. This study demonstrates that,
       in the absence of virus infection and even in the absence of distinct
       viral tropism, human glia respond like rodent glia to non-CD4-binding
       epitopes of gp120/gp41 with cytokine and nitric oxide production.
       Differences among fetal, neonatal, and adult glial cells' infectivity
       and cytokine production indicate that, in addition to functional
       differences of glia at different stages of development, cofactors in
       vitro and in vivo may also be critical in facilitating the biological
       responses of these cells to HIV-1.
 DE    Adolescence  Adult  Aging  Brain/CYTOLOGY/*IMMUNOLOGY/VIROLOGY  Child,
       Preschool  Comparative Study  Cytokines/*BIOSYNTHESIS  Epitopes  Gene
       Expression Regulation  Gene Products, env/*IMMUNOLOGY  Human  HIV
       Envelope Protein gp120/IMMUNOLOGY  HIV Envelope Protein gp41/IMMUNOLOGY
       HIV-1/GROWTH & DEVELOPMENT/*IMMUNOLOGY  Infant
       Interleukin-1/BIOSYNTHESIS  Neuroglia/CYTOLOGY/*IMMUNOLOGY/VIROLOGY
       Nitric Oxide/*BIOSYNTHESIS  Polymerase Chain Reaction  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Tumor Necrosis Factor/BIOSYNTHESIS
       JOURNAL ARTICLE

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

