title: Herpes simplex virus type 1 immediate-early protein ICP27 is required for efficient incorporation of ICP0 and ICP4 into virions.
abstract: Early in infection, herpes simplex virus type 1 (HSV-1) immediate-early (IE) proteins ICP0 and ICP4 localize to the nucleus, where they stimulate viral transcription. Later in infection, ICP0 and to a lesser extent ICP4 accumulate in the cytoplasm, but their biological role there is unknown. Previously, it was shown that the cytoplasmic localization of ICP0/4 requires the multifunctional IE protein ICP27, which is itself an activator of viral gene expression. Here, we identify a viral ICP27 mutant, d3-4, which is unable to efficiently localize ICP0 and ICP4 to the cytoplasm but which otherwise resembles wild-type HSV-1 in its growth and viral gene expression phenotypes. These results genetically separate the function of ICP27 that affects ICP0/4 localization from its other functions, which affect viral growth and gene expression. As both ICP0 and ICP4 are known to be minor virion components, we used d3-4 to test the hypothesis that the cytoplasmic localization of these proteins is required for their incorporation into viral particles. Consistent with this conjecture, d3-4 virions were found to lack ICP0 in their tegument and to have greatly reduced levels of ICP4. Thus, the cytoplasmic localization of ICP0 and ICP4 appears to be a prerequisite for the assembly of these important transcriptional regulatory proteins into viral particles. Furthermore, our results show that ICP27 plays a previously unrecognized role in determining the composition of HSV-1 virions.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Mayo Mail Code 196, 420 Delaware St. S.E., Minneapolis, MN 55455, USA.
authors.forename: Lenka
authors.initials: L
authors.lastname: Sedlackova
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Rice
mesh_terms: D003593:Cytoplasm / Q000737:chemistry; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014771:Virion / Q000737:chemistry*; D019065:Virus Assembly / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D050505:Mutant Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1