PMID- 16973544 OWN - NLM STAT- MEDLINE DCOM- 20061024 LR - 20191210 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 80 IP - 19 DP - 2006 Oct TI - ICP22 is required for wild-type composition and infectivity of herpes simplex virus type 1 virions. PG - 9381-90 AB - 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. FAU - Orlando, Joseph S AU - Orlando JS AD - 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. FAU - Balliet, John W AU - Balliet JW FAU - Kushnir, Anna S AU - Kushnir AS FAU - Astor, Todd L AU - Astor TL FAU - Kosz-Vnenchak, Magdalena AU - Kosz-Vnenchak M FAU - Rice, Stephen A AU - Rice SA FAU - Knipe, David M AU - Knipe DM FAU - Schaffer, Priscilla A AU - Schaffer PA LA - eng GR - R01 CA20260/CA/NCI NIH HHS/United States GR - F32 CA99887/CA/NCI NIH HHS/United States GR - R01 CA020260/CA/NCI NIH HHS/United States GR - F32 CA099887/CA/NCI NIH HHS/United States GR - R01 AI50127/AI/NIAID NIH HHS/United States GR - R01 AI050127/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (ICP22 protein, human herpesvirus 1) RN - 0 (Immediate-Early Proteins) RN - 0 (Viral Regulatory and Accessory Proteins) SB - IM MH - Animals MH - Cell Line MH - Chlorocebus aethiops MH - Genome, Viral/genetics MH - Herpes Simplex/genetics/pathology/*virology MH - Herpesvirus 1, Human/*chemistry/*physiology MH - Humans MH - Immediate-Early Proteins/isolation & purification/*metabolism MH - Kinetics MH - Male MH - Mice MH - Mutation/genetics MH - Trigeminal Ganglion/metabolism/pathology/virology MH - Viral Regulatory and Accessory Proteins MH - Virion/*chemistry/genetics/isolation & purification/*physiology PMC - PMC1617265 EDAT- 2006/09/16 09:00 MHDA- 2006/10/25 09:00 PMCR- 2007/02/01 CRDT- 2006/09/16 09:00 PHST- 2006/09/16 09:00 [pubmed] PHST- 2006/10/25 09:00 [medline] PHST- 2006/09/16 09:00 [entrez] PHST- 2007/02/01 00:00 [pmc-release] AID - 80/19/9381 [pii] AID - 1061-06 [pii] AID - 10.1128/JVI.01061-06 [doi] PST - ppublish SO - J Virol. 2006 Oct;80(19):9381-90. doi: 10.1128/JVI.01061-06.