title: Herpes simplex virus type 1 virion-derived US11 inhibits type 1 interferon-induced protein kinase R phosphorylation.
abstract: The herpes simplex virus type 1 (HSV-1) VRTK(-) strain that was previously isolated in our laboratory as an acyclovir-resistant thymidine kinase (TK)-deficient mutant, is more sensitive to type 1 interferon than is the parent strain VR3. The properties of this mutant were investigated to clarify the mechanism for its hyper-sensitivity to interferon (IFN). It was found that: (i) IFN-pretreated cells, but not those treated with IFN after adsorption, are hyper-sensitive to IFN; (ii) the mutant cannot inhibit protein kinase R phosphorylation efficiently during the early stage of replication (2 hrs post-infection); (iii) expression of US11 in infected cells and its incorporation into the virion is reduced in the mutant compared to the wild type, despite the fact that a similar degree of DNA synthesis occurs during replication of both strains and; (iv) over-expression of wild-type viral TK has no effect on the phenotype of the VRTK(-) strain, indicating that the phenotype is induced by a mutation(s) that does not involve the TK gene. These results suggested that the presence of US11 in the virion, but not that expressed after infection, plays an important role in the escape function of HSV-1 from the antiviral activity of type 1 IFN.
authors.affiliation: Department of Microbiology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishioka
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Kaneko
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sorimachi
authors.forename: Eiko
authors.initials: E
authors.lastname: Fukushima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suzutani
mesh_terms: D000818:Animals; D002460:Cell Line; D018259:Herpesvirus 1, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007372:Interferons / Q000276:immunology*; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; D007372:Interferons; D019892:eIF-2 Kinase