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M9630074.TXT
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1996-02-27
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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).