The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes.
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.
Lin
Rongtuan
R
Lady Davis Research Institute, Montreal H3T 1E2, Canada.
Noyce
Ryan S
RS
Collins
Susan E
SE
Everett
Roger D
RD
Mossman
Karen L
KL
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006561:Herpes Simplex / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000502:physiology*; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007372:Interferons / Q000494:pharmacology*; D012260:Ribonucleases; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000502:physiology; D016335:Zinc Fingers
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; C494234:IRF7 protein, human; D017874:Immediate-Early Proteins; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D014157:Transcription Factors; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D007372:Interferons; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D012260:Ribonucleases