       Document 0101
 DOCN  M9460101
 TI    Cytokine-mediated induction of human immunodeficiency virus (HIV)
       expression and cell death in chronically infected U1 cells: do tumor
       necrosis factor alpha and gamma interferon selectively kill HIV-infected
       cells?
 DT    9404
 AU    Biswas P; Poli G; Orenstein JM; Fauci AS; Laboratory of
       Immunoregulation, National Institute of Allergy and; Infectious
       Diseases, National Institutes of Health, Bethesda,; Maryland 20892.
 SO    J Virol. 1994 Apr;68(4):2598-604. Unique Identifier : AIDSLINE
       MED/94187101
 AB    Infection with several DNA or RNA viruses induces a state of increased
       sensitivity to cell lysis mediated by tumor necrosis factor (TNF),
       particularly in the presence of gamma interferon (IFN-gamma). Infection
       of human cells with the human immunodeficiency virus (HIV) may induce a
       similar phenomenon. However, TNF and IFN-gamma are known upregulators of
       HIV replication, raising the question of the potential role of these
       cytokines in the selective elimination of cells infected with this
       virus. The present study demonstrates that chronically infected U1 cells
       were killed with much greater efficiency by costimulation with TNF-alpha
       and IFN-gamma than their uninfected parental cell line U937. However,
       synergistic induction of viral expression also occurred in U1 cells as a
       consequence of treatment with the two cytokines. Cell death in U1 cells
       was not caused by the massive production of virions, in that
       costimulation with glucocorticoid hormones and TNF-alpha or IFN-gamma
       resulted in high levels of virion production without cytopathicity. To
       investigate the nature of the selective cytotoxic effect observed in U1
       cells costimulated with TNF-alpha plus IFN-gamma, a panel of uninfected
       cell clones was generated by limiting dilution of U937 cells and tested
       for response to TNF-alpha and/or IFN-gamma. In contrast to the uncloned
       bulk parental U937 cell line, most uninfected cell clones showed a very
       high susceptibility to being killed by TNF-alpha and IFN-gamma. Similar
       findings were obtained when both infected U1 cells and several
       uninfected U937 cell clones were costimulated with an anti-Fas
       monoclonal antibody in the presence of IFN-gamma, although, unlike cells
       stimulated with TNF-alpha, cells treated with anti-Fas antibody did not
       express virus. Therefore, the increased susceptibility to
       cytokine-mediated lysis observed in cell lines infected with HIV is
       likely due to the selection of preexisting cell clones rather than viral
       infection.
 DE    Antibodies, Monoclonal/PHARMACOLOGY  Antigens, Surface/IMMUNOLOGY  Cell
       Death/*DRUG EFFECTS  Cell Membrane/CHEMISTRY  Clone Cells/*MICROBIOLOGY
       Drug Synergism  Human  HIV/*GROWTH & DEVELOPMENT  Interferon Type
       II/*PHARMACOLOGY  Receptors, Interferon/ANALYSIS  Receptors, Tumor
       Necrosis Factor/ANALYSIS  Support, Non-U.S. Gov't  Tumor Necrosis
       Factor/*PHARMACOLOGY  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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

