       Document 0074
 DOCN  M9630074
 TI    Human immunodeficiency virus 1 envelope-initiated G2-phase programmed
       cell death.
 DT    9603
 AU    Kolesnitchenko V; Wahl LM; Tian H; Sunila I; Tani Y; Hartmann DP;
       Cossman J; Raffeld M; Orenstein J; Samelson LE; et al; Cell Biology and
       Metabolism Branch, National Institute of Child; Health and Human
       Development, National Institutes of Health,; Bethesda, MD 20892, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11889-93. Unique Identifier
       : AIDSLINE MED/96102220
 AB    Despite intensive investigation, no clearly defined mechanism explaining
       human immunodeficiency virus (HIV)-induced cell killing has emerged.
       HIV-1 infection is initiated through a high-affinity interaction between
       the HIV-1 external envelope glycoprotein (gp120) and the CD4 receptor on
       T cells. Cell killing is a later event intimately linked by in vitro
       genetic analyses with the fusogenic properties of the HIV envelope
       glycoprotein gp120 and transmembrane glycoprotein gp41. In this report,
       we describe aberrancies in cell cycle regulatory proteins initiated by
       cell-cell contact between T cells expressing HIV-1 envelope
       glycoproteins and other T cells expressing CD4 receptors. Cells rapidly
       accumulate cyclin B protein and tyrosine-hyperphosphorylated p34cdc2
       (cdk1) kinase, indicative of cell cycle arrest at G2 phase. Moreover,
       these cells continue to synthesize cyclin B protein, enlarge and display
       an abnormal ballooned morphology, and disappear from the cultures in a
       pattern previously described for cytotoxicity induced by DNA synthesis
       (S phase) inhibitors. Similar changes are observed in peripheral blood
       mononuclear cells infected in vitro with pathogenic primary isolates of
       HIV-1.
 DE    Antigens, CD4/METABOLISM  *Apoptosis  Cell Communication  Cell
       Separation/METHODS  Cyclins/METABOLISM  Cytopathogenic Effect, Viral
       CD4-Positive T-Lymphocytes/IMMUNOLOGY  Fluorescent Antibody Technique
       *G2 Phase  Human  *HIV Envelope Protein gp120  HIV Infections/*PATHOLOGY
       *HIV-1/ISOLATION & PURIF  Leukocytes, Mononuclear/PATHOLOGY
       Phosphorylation  Protein p34cdc2/METABOLISM
       T-Lymphocytes/IMMUNOLOGY/*PATHOLOGY  JOURNAL ARTICLE

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

