title: ICP0 prevents RNase L-independent rRNA cleavage in herpes simplex virus type 1-infected cells.
abstract: The classical interferon (IFN)-dependent antiviral response to viral infection involves the regulation of IFN-stimulated genes (ISGs), one being the gene encoding cellular endoribonuclease RNase L, which arrests protein synthesis and induces apoptosis by nonspecifically cleaving rRNA. Recently, the herpes simplex virus type 1 (HSV-1) protein ICP0 has been shown to block the induction of ISGs by subverting the IFN pathway upstream of the 2'-5'-oligoadenylate synthetase (OAS)/RNase L pathway. We report that ICP0 also prevents rRNA degradation at late stages of HSV-1 infection, independent of its E3 ubiquitin ligase activity, and that the resultant rRNA degradation is independent of the classical RNase L antiviral pathway. Moreover, the degradation is independent of the viral RNase vhs and is independent of IFN response factor 3. These studies indicate the existence of another, previously unidentified, RNase that is part of the host antiviral response to viral infection.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sobol
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mossman
mesh_terms: D004722:Endoribonucleases / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D012335:RNA, Ribosomal; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease