title: Herpes simplex virus immediate-early protein ICP22 triggers loss of serine 2-phosphorylated RNA polymerase II.
abstract: During eukaryotic mRNA transcription, the synthetic activity and mRNA processing factor interactions of RNA polymerase II (RNAP II) are regulated by phosphorylation of its carboxyl-terminal domain (CTD), with modification occurring primarily on serines 2 and 5 of the CTD. We previously showed that herpes simplex virus type 1 (HSV-1) infection rapidly triggers the loss of RNAP II forms bearing serine 2 phosphorylation (Ser-2P RNAP II). Here we show that the HSV-1 immediate-early (IE) protein ICP22 is responsible for this effect during the IE phase of infection. This activity does not require the viral UL13 protein kinase, which is required for several other regulatory functions of ICP22. Additionally, we show that transient expression of ICP22 can trigger the loss of Ser-2P RNAP II in transfected cells. Thus, the ability of ICP22 to cause the loss of Ser-2 RNAP II does not require other viral factors or the context of the infected cell. Expression of the HSV-1 ICP22-related protein US1.5, which corresponds to residues 147 to 420 of ICP22, also triggers a loss of Ser-2P RNAP II in transfected cells, whereas expression of the varicella-zoster virus ICP22 homolog, ORF63, does not. Our study also provides evidence for a second, viral late gene-dependent pathway that triggers loss of Ser-2P RNAP II in infected cells, consistent with the recent work of Dai-Ju et al. (J. Q. Dai-Ju, L. Li, L. A. Johnson, and R. M. Sandri-Goldin, J. Virol. 80:3567-3581, 2006). Therefore, it appears that HSV-1 has evolved redundant mechanisms for triggering the loss of a specific phosphorylated form of RNAP II.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Fraser
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Rice
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000502:physiology*; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D012319:RNA Polymerase II / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C074551:immediate early protein 63, Human herpesvirus 3; D012694:Serine; D011494:Protein Kinases; C082380:UL13 protein, Simplexvirus; D012319:RNA Polymerase II