title: Varicella-zoster virus (VZV) ORF17 protein induces RNA cleavage and is critical for replication of VZV at 37 degrees C but not 33 degrees C.
abstract: Varicella-zoster virus (VZV) open reading frame 17 (ORF17) is homologous to herpes simplex virus (HSV) UL41, which encodes the viral host shutoff protein (vhs). HSV vhs induces degradation of mRNA and rapid shutoff of host protein synthesis. An antibody to ORF17 protein detected a 46-kDa protein in VZV-infected cells. While HSV vhs is located in virions, VZV ORF17 protein was not detectable in virions. ORF17 protein induced RNA cleavage, but to a substantially lesser extent than HSV-1 vhs. Expression of ORF17 protein did not inhibit expression from a beta-galactosidase reporter plasmid, while HSV type 1 vhs abolished reporter expression. Two VZV ORF17 deletion mutants were constructed to examine the role of ORF17 in virus replication. While the ORF17 VZV mutants grew to peak titers that were similar to those of the parental virus at 33 degrees C, the ORF17 mutants grew to 20- to 35-fold-lower titers than parental virus at 37 degrees C. ORF62 protein was distributed in a different pattern in the nuclei and cytoplasm of cells infected with an ORF17 deletion mutant at 37 degrees C compared to 33 degrees C. Inoculation of cotton rats with the ORF17 deletion mutant resulted in a level of latent infection similar to that produced by inoculation with the parental virus. The importance of ORF17 protein for viral replication at 37 degrees C but not at 33 degrees C suggests that this protein may facilitate the growth of virus in certain tissues in vivo.
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015870:Gene Expression; D017930:Genes, Reporter; D018259:Herpesvirus 1, Human / Q000378:metabolism; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D016296:Mutagenesis; D016366:Open Reading Frames; D012315:RNA Caps / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D012260:Ribonucleases; D013696:Temperature; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; C468297:ORF17 protein, varicella-zoster virus; D012315:RNA Caps; D012367:RNA, Viral; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C056913:glycoprotein E, varicella-zoster virus; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases; D001616:beta-Galactosidase