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?

Priscilla Biswas, Guido Poli, Jan M. Orenstein, Anthony S. Fauci

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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-γ). Infection of human cells with the human immunodeficiency virus (HIV) may induce a similar phenomenon. However, TNF and IFN-γ 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-α and IFN-γ 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-γ or IFN-γ 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-α plus IFN-γ, a panel of uninfected cell clones was generated by limiting dilution of U937 cells and tested for response to TNF-α and/or IFN-γ. In contrast to the uncloned bulk parental U937 cell line, most uninfected cell clones showed a very high susceptibility to being killed by TNF-α and IFN-γ. 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-γ, although, unlike cells stimulated with TNF-α, 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.

Original languageEnglish
Pages (from-to)2598-2604
Number of pages7
JournalJournal of Virology
Volume68
Issue number4
Publication statusPublished - Apr 1994

Fingerprint

interferon-alpha
Human immunodeficiency virus
interferon-gamma
Interferon-alpha
tumor necrosis factor-alpha
Interferon-gamma
cell death
Cell Death
cytokines
Tumor Necrosis Factor-alpha
HIV
Cytokines
Interferons
tumor necrosis factors
interferons
U937 Cells
cells
Clone Cells
anti-Fas monoclonal antibody
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

@article{747694ab3ce0473794117bcbdb881c6d,
title = "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?",
abstract = "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-γ). Infection of human cells with the human immunodeficiency virus (HIV) may induce a similar phenomenon. However, TNF and IFN-γ 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-α and IFN-γ 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-γ or IFN-γ 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-α plus IFN-γ, a panel of uninfected cell clones was generated by limiting dilution of U937 cells and tested for response to TNF-α and/or IFN-γ. In contrast to the uncloned bulk parental U937 cell line, most uninfected cell clones showed a very high susceptibility to being killed by TNF-α and IFN-γ. 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-γ, although, unlike cells stimulated with TNF-α, 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.",
author = "Priscilla Biswas and Guido Poli and Orenstein, {Jan M.} and Fauci, {Anthony S.}",
year = "1994",
month = "4",
language = "English",
volume = "68",
pages = "2598--2604",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Cytokine-mediated induction of Human Immunodeficiency Virus (HIV) expression and cell death in chronically infected U1 cells

T2 - Do tumor necrosis factor alpha and gamma interferon selectively kill HIV-infected cells?

AU - Biswas, Priscilla

AU - Poli, Guido

AU - Orenstein, Jan M.

AU - Fauci, Anthony S.

PY - 1994/4

Y1 - 1994/4

N2 - 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-γ). Infection of human cells with the human immunodeficiency virus (HIV) may induce a similar phenomenon. However, TNF and IFN-γ 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-α and IFN-γ 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-γ or IFN-γ 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-α plus IFN-γ, a panel of uninfected cell clones was generated by limiting dilution of U937 cells and tested for response to TNF-α and/or IFN-γ. In contrast to the uncloned bulk parental U937 cell line, most uninfected cell clones showed a very high susceptibility to being killed by TNF-α and IFN-γ. 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-γ, although, unlike cells stimulated with TNF-α, 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.

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-γ). Infection of human cells with the human immunodeficiency virus (HIV) may induce a similar phenomenon. However, TNF and IFN-γ 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-α and IFN-γ 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-γ or IFN-γ 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-α plus IFN-γ, a panel of uninfected cell clones was generated by limiting dilution of U937 cells and tested for response to TNF-α and/or IFN-γ. In contrast to the uncloned bulk parental U937 cell line, most uninfected cell clones showed a very high susceptibility to being killed by TNF-α and IFN-γ. 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-γ, although, unlike cells stimulated with TNF-α, 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.

UR - http://www.scopus.com/inward/record.url?scp=0028219305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028219305&partnerID=8YFLogxK

M3 - Article

C2 - 7511175

AN - SCOPUS:0028219305

VL - 68

SP - 2598

EP - 2604

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 4

ER -