Role for herpes simplex virus 1 ICP27 in the inhibition of type I interferon signaling.
Host cells respond to viral infection by many mechanisms, including the production of type I interferons which act in a paracrine and autocrine manner to induce the expression of antiviral interferon-stimulated genes (ISGs). Viruses have evolved means to inhibit interferon signaling to avoid induction of the innate immune response. Herpes simplex virus 1 (HSV-1) has several mechanisms to inhibit type I interferon production, the activities of ISGs, and the interferon signaling pathway itself. We report that the inhibition of the Jak/STAT pathway by HSV-1 requires viral gene expression and that viral immediate-early protein ICP27 plays a role in downregulating STAT-1 phosphorylation and in preventing the accumulation of STAT-1 in the nucleus. We also show that expression of ICP27 by transfection causes an inhibition of IFN-induced STAT-1 nuclear accumulation. Therefore, ICP27 is necessary and sufficient for at least some of the effects of HSV infection on STAT-1.
Johnson
Karen E
KE
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston 02115, USA.
Song
Byeongwoon
B
Knipe
David M
DM
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D016898:Interferon-alpha; D009154:Mutation; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014709:Vero Cells
C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D007370:Interferon Type I; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor