Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT1 and NF-kB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus

Surendran Mahalingam, Brett Lidbury

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    68 Citations (Scopus)

    Abstract

    Subneutralizing concentrations of antibody may enhance virus infection by bringing the virus-antibody complex into contact with the cell surface Fc receptors; this interaction facilitates entry of virus into the cell and is referred to as antibody-dependent enhancement (ADE) of infection. Northern analysis of macrophage RNA demonstrated that ADE infection by the indigenous Australian alphavirus Ross River (RRV-ADE) ablated or diminished message for tumor necrosis factor alpha (TNF-alpha), nitric-oxide synthase 2 (NOS2), and IFN regulatory factor 1 (IRF-1), as well as for IFN-inducible protein 10 (IP-10) and IFN-beta; the transcription of a control gene was unaffected. Additionally, electrophoretic mobility-shift assay (EMSA) studies showed that transcription factor IFN-alpha-activated factor (AAF), IFN-stimulated gene factor 3 (ISGF3), and nuclear factor-kappaB (NF-kappaB) complex formation in macrophage nuclear extracts were specifically suppressed post-RRV-ADE infection, emphasizing the capacity for ADE infections to compromise antiviral responses at the transcriptional level. The suppression of antiviral transcription factor complexes was shown to depend on replicating virus and was not simply a result of general antibody-Fc-receptor interaction. Although only a minority of cells ( approximately 15%) were shown to be positive for RRV by immunostaining techniques post ADE, molecular (RT-PCR) analysis showed that unstained cells carried RRV-RNA, indicating a higher level of viral infectivity than previously suspected. Electron microscopy studies confirmed this observation. Furthermore, levels of cellular IL-10 protein were dramatically elevated in RRV-ADE cultures. This evidence demonstrates that RRV can potently disrupt the activation of specific antiviral pathways via ADE infection pathways, and may suggest a significant mechanism in the infection and pathogenesis of other ADE viruses
    Original languageEnglish
    Pages (from-to)13819-13824
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume99
    Issue number21
    DOIs
    Publication statusPublished - 2002

    Fingerprint

    Antibody-Dependent Enhancement
    Ross River virus
    NF-kappa B
    Antiviral Agents
    Lipopolysaccharides
    Macrophages
    Infection
    Fc Receptors
    Viruses
    Antibodies
    Transcription Factors
    Post and Core Technique
    RNA
    Alphavirus
    Virus Internalization
    Cell Surface Receptors
    Electrophoretic Mobility Shift Assay
    Virus Diseases
    Rivers
    Nitric Oxide Synthase

    Cite this

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    title = "Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT1 and NF-kB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus",
    abstract = "Subneutralizing concentrations of antibody may enhance virus infection by bringing the virus-antibody complex into contact with the cell surface Fc receptors; this interaction facilitates entry of virus into the cell and is referred to as antibody-dependent enhancement (ADE) of infection. Northern analysis of macrophage RNA demonstrated that ADE infection by the indigenous Australian alphavirus Ross River (RRV-ADE) ablated or diminished message for tumor necrosis factor alpha (TNF-alpha), nitric-oxide synthase 2 (NOS2), and IFN regulatory factor 1 (IRF-1), as well as for IFN-inducible protein 10 (IP-10) and IFN-beta; the transcription of a control gene was unaffected. Additionally, electrophoretic mobility-shift assay (EMSA) studies showed that transcription factor IFN-alpha-activated factor (AAF), IFN-stimulated gene factor 3 (ISGF3), and nuclear factor-kappaB (NF-kappaB) complex formation in macrophage nuclear extracts were specifically suppressed post-RRV-ADE infection, emphasizing the capacity for ADE infections to compromise antiviral responses at the transcriptional level. The suppression of antiviral transcription factor complexes was shown to depend on replicating virus and was not simply a result of general antibody-Fc-receptor interaction. Although only a minority of cells ( approximately 15{\%}) were shown to be positive for RRV by immunostaining techniques post ADE, molecular (RT-PCR) analysis showed that unstained cells carried RRV-RNA, indicating a higher level of viral infectivity than previously suspected. Electron microscopy studies confirmed this observation. Furthermore, levels of cellular IL-10 protein were dramatically elevated in RRV-ADE cultures. This evidence demonstrates that RRV can potently disrupt the activation of specific antiviral pathways via ADE infection pathways, and may suggest a significant mechanism in the infection and pathogenesis of other ADE viruses",
    author = "Surendran Mahalingam and Brett Lidbury",
    year = "2002",
    doi = "10.1073/pnas.202415999",
    language = "English",
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    pages = "13819--13824",
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    T1 - Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT1 and NF-kB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus

    AU - Mahalingam, Surendran

    AU - Lidbury, Brett

    PY - 2002

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    N2 - Subneutralizing concentrations of antibody may enhance virus infection by bringing the virus-antibody complex into contact with the cell surface Fc receptors; this interaction facilitates entry of virus into the cell and is referred to as antibody-dependent enhancement (ADE) of infection. Northern analysis of macrophage RNA demonstrated that ADE infection by the indigenous Australian alphavirus Ross River (RRV-ADE) ablated or diminished message for tumor necrosis factor alpha (TNF-alpha), nitric-oxide synthase 2 (NOS2), and IFN regulatory factor 1 (IRF-1), as well as for IFN-inducible protein 10 (IP-10) and IFN-beta; the transcription of a control gene was unaffected. Additionally, electrophoretic mobility-shift assay (EMSA) studies showed that transcription factor IFN-alpha-activated factor (AAF), IFN-stimulated gene factor 3 (ISGF3), and nuclear factor-kappaB (NF-kappaB) complex formation in macrophage nuclear extracts were specifically suppressed post-RRV-ADE infection, emphasizing the capacity for ADE infections to compromise antiviral responses at the transcriptional level. The suppression of antiviral transcription factor complexes was shown to depend on replicating virus and was not simply a result of general antibody-Fc-receptor interaction. Although only a minority of cells ( approximately 15%) were shown to be positive for RRV by immunostaining techniques post ADE, molecular (RT-PCR) analysis showed that unstained cells carried RRV-RNA, indicating a higher level of viral infectivity than previously suspected. Electron microscopy studies confirmed this observation. Furthermore, levels of cellular IL-10 protein were dramatically elevated in RRV-ADE cultures. This evidence demonstrates that RRV can potently disrupt the activation of specific antiviral pathways via ADE infection pathways, and may suggest a significant mechanism in the infection and pathogenesis of other ADE viruses

    AB - Subneutralizing concentrations of antibody may enhance virus infection by bringing the virus-antibody complex into contact with the cell surface Fc receptors; this interaction facilitates entry of virus into the cell and is referred to as antibody-dependent enhancement (ADE) of infection. Northern analysis of macrophage RNA demonstrated that ADE infection by the indigenous Australian alphavirus Ross River (RRV-ADE) ablated or diminished message for tumor necrosis factor alpha (TNF-alpha), nitric-oxide synthase 2 (NOS2), and IFN regulatory factor 1 (IRF-1), as well as for IFN-inducible protein 10 (IP-10) and IFN-beta; the transcription of a control gene was unaffected. Additionally, electrophoretic mobility-shift assay (EMSA) studies showed that transcription factor IFN-alpha-activated factor (AAF), IFN-stimulated gene factor 3 (ISGF3), and nuclear factor-kappaB (NF-kappaB) complex formation in macrophage nuclear extracts were specifically suppressed post-RRV-ADE infection, emphasizing the capacity for ADE infections to compromise antiviral responses at the transcriptional level. The suppression of antiviral transcription factor complexes was shown to depend on replicating virus and was not simply a result of general antibody-Fc-receptor interaction. Although only a minority of cells ( approximately 15%) were shown to be positive for RRV by immunostaining techniques post ADE, molecular (RT-PCR) analysis showed that unstained cells carried RRV-RNA, indicating a higher level of viral infectivity than previously suspected. Electron microscopy studies confirmed this observation. Furthermore, levels of cellular IL-10 protein were dramatically elevated in RRV-ADE cultures. This evidence demonstrates that RRV can potently disrupt the activation of specific antiviral pathways via ADE infection pathways, and may suggest a significant mechanism in the infection and pathogenesis of other ADE viruses

    U2 - 10.1073/pnas.202415999

    DO - 10.1073/pnas.202415999

    M3 - Article

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    JO - National Academy of Sciences. Proceedings

    JF - National Academy of Sciences. Proceedings

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    ER -