Abstract
Virus infection induces a rapid cellular response in cells characterized by the induction of interferon. While interferon itself does not induce an antiviral response, it activates a number of interferon-stimulated genes that collectively function to inhibit virus replication and spread. Previously, we and others reported that herpes simplex virus type 1 (HSV-1) induces an interferon -independent antiviral response in the absence of virus replication. Here, we report that the HSV-1 proteins ICP0 and vhs function in concert to disable the host antiviral response. In particular, we show that ICP0 blocks interferon regulatory factor IRF3- and IRF7-mediated activation of interferon-stimulated genes and that the RING finger domain of ICP0 is essential for this activity. Furthermore, we demonstrate that HSV-1 modifies the IRF3 pathway in a manner different from that of the small RNA viruses most commonly studied.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / pharmacology
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Cell Line
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation*
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Herpes Simplex / immunology
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Herpes Simplex / virology
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Herpesvirus 1, Human / immunology
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Herpesvirus 1, Human / physiology*
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Humans
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Immediate-Early Proteins / chemistry
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Immediate-Early Proteins / physiology*
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferons / pharmacology*
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Ribonucleases
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Transcription Factors / metabolism*
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Ubiquitin-Protein Ligases
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Viral Proteins / physiology
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Zinc Fingers
Substances
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Antiviral Agents
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DNA-Binding Proteins
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IRF3 protein, human
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IRF7 protein, human
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Immediate-Early Proteins
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Transcription Factors
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Viral Proteins
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virion host shutoff protein, Simplexvirus
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Interferons
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Ubiquitin-Protein Ligases
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Vmw110 protein, Human herpesvirus 1
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Ribonucleases