title: ICP22 is required for wild-type composition and infectivity of herpes simplex virus type 1 virions.
abstract: The immediate-early regulatory protein ICP22 is required for efficient replication of herpes simplex virus type 1 in some cell types (permissive) but not in others (restrictive). In mice infected via the ocular route, the pathogenesis of an ICP22- virus, 22/n199, was altered relative to that of wild-type virus. Specifically, tear film titers of 22/n199-infected mice were significantly reduced at 3 h postinfection relative to those of mice infected with wild-type virus. Further, 22/n199 virus titers were below the level of detection in trigeminal ganglia (TG) during the first 9 days postinfection. On day 30 postinfection, TG from 22/n199-infected mice contained reduced viral genome loads and exhibited reduced expression of latency-associated transcripts and reduced reactivation efficiency relative to TG from wild-type virus-infected mice. Notably, the first detectable alteration in the pathogenesis of 22/n199 in these tests occurred in the eye prior to the onset of nascent virus production. Thus, ICP22- virions appeared to be degraded, cleared, or adsorbed more rapidly than wild-type virions, implying potential differences in the composition of the two virion types. Analysis of the protein composition of purified extracellular virions indicated that ICP22 is not a virion component and that 22/n199 virions sediment at a reduced density relative to wild-type virions. Although similar to wild-type virions morphologically, 22/n199 virions contain reduced amounts of two gamma2 late proteins, US11 and gC, and increased amounts of two immediate-early proteins, ICP0 and ICP4, as well as protein species not detected in wild-type virions. Although ICP22- viruses replicate to near-wild-type levels in permissive cells, the virions produced in these cells are biochemically and physically different from wild-type virions. These virion-specific differences in ICP22- viruses add a new level of complexity to the functional analysis of this immediate-early viral regulatory protein.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School at the Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN 123, Boston, MA 02215, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Orlando
authors.forename: John W
authors.initials: JW
authors.lastname: Balliet
authors.forename: Anna S
authors.initials: AS
authors.lastname: Kushnir
authors.forename: Todd L
authors.initials: TL
authors.lastname: Astor
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kosz-Vnenchak
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Rice
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D016679:Genome, Viral / Q000235:genetics; D006561:Herpes Simplex / Q000235:genetics / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000473:pathology / Q000821:virology; D054334:Viral Regulatory and Accessory Proteins; D014771:Virion / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
chemical_list: C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D054334:Viral Regulatory and Accessory Proteins