title: Selective degradation of mRNAs by the HSV host shutoff RNase is regulated by the UL47 tegument protein.
abstract: Herpes simplex virus 1 (HSV-1) encodes an endoribonuclease that is responsible for the shutoff of host protein synthesis [virion host shutoff (VHS)-RNase]. The VHS-RNase released into cells during infection targets differentially four classes of mRNAs. Thus, (a) VHS-RNase degrades stable cellular mRNAs and α (immediate early) viral mRNAs; (b) it stabilizes host stress response mRNAs after deadenylation and subsequent cleavage near the adenylate-uridylate (AU)-rich elements; (c) it does not effectively degrade viral β or γ mRNAs; and (d) it selectively spares from degradation a small number of cellular mRNAs. Current evidence suggests that several viral and at least one host protein (tristetraprolin) regulate its activity. Thus, virion protein (VP) 16 and VP22 neutralize the RNase activity at late times after infection. By binding to AU-rich elements via its interaction with tristetraprolin, the RNase deadenylates and cleaves the mRNAs in proximity to the AU-rich elements. In this report we show that another virion protein, UL47, brought into the cell during infection, attenuates the VHS-RNase activity with respect to stable host and viral α mRNAs and effectively blocks the degradation of β and γ mRNAs, but it has no effect on the processing of AU-rich mRNAs. The properties of UL47 suggest that it, along with the α protein infected cell protein 27, attenuates degradation of mRNAs by the VHS-RNase through interaction with the enzyme in polyribosomes. Mutants lacking both VHS-RNase and UL47 overexpress α genes and delay the expression of β and γ genes, suggesting that overexpression of α genes inhibits the downstream expression of early and late genes.
authors.affiliation: Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Minfeng
authors.initials: M
authors.lastname: Shu
authors.forename: Brunella
authors.initials: B
authors.lastname: Taddeo
authors.forename: Weiran
authors.initials: W
authors.lastname: Zhang
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
mesh_terms: D063307:AU Rich Elements / Q000235:genetics; D000818:Animals; D002457:Cell Extracts; D004279:DNA, Viral / Q000378:metabolism; D017353:Gene Deletion; D057809:HEK293 Cells; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism; D015203:Reproducibility of Results; D012260:Ribonucleases / Q000378:metabolism*; D014162:Transfection; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D002457:Cell Extracts; D004279:DNA, Viral; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D012367:RNA, Viral; C085822:VP13-14 protein, herpes simplex virus type 1; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases