title: Herpes simplex virus type 1 suppresses the interferon signaling pathway by inhibiting phosphorylation of STATs and janus kinases during an early infection stage.
abstract: We examined the influence on the interferon (IFN) signaling pathway of infection with herpes simplex virus type 1 (HSV-1) strain VR3. Data from reporter gene assays showed that expression of both type I and type II IFN-inducible genes was dramatically suppressed during the early stage of HSV-1 infection (2 to 3 h postinfection). During these periods, phosphorylation levels of janus kinases (JAKs) and STATs did not increase after treatment of HSV-1-infected FL cells with IFN-alpha or IFN-gamma, although cellular protein levels of the JAKs and the STATs were not significantly changed. In contrast, the inhibitory effect of HSV-1 on phosphorylation of STAT1 was not observed in U937 cells, which show resistance to steady-state accumulation of RNA for HSV-1 immediate-early genes. The phosphorylation of STAT1 in FL cells was not inhibited by infection with a UV-inactivated virus. These results indicate that viral gene expression or viral protein production is necessary for the inhibition of phosphorylation by HSV-1.
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, 060-8556, Japan. syokota@sapmed.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: N
authors.initials: N
authors.lastname: Yokosawa
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Suzutani
authors.forename: I
authors.initials: I
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Jimbow
authors.forename: N
authors.initials: N
authors.lastname: Fujii
mesh_terms: D004268:DNA-Binding Proteins / Q000502:physiology*; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000502:physiology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D020298:U937 Cells; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D007372:Interferons; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2