ICP22 is required for wild-type composition and infectivity of herpes simplex virus type 1 virions

Joseph S. Orlando, John W. Balliet, Anna S. Kushnir, Todd L. Astor, Magdalena Kosz-Vnenchak, Stephen A. Rice, David M. Knipe, Priscilla A. Schaffer

Research output: Contribution to journalArticle

25 Scopus citations

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 γ2 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.

Original languageEnglish (US)
Pages (from-to)9381-9390
Number of pages10
JournalJournal of virology
Volume80
Issue number19
DOIs
StatePublished - Oct 2006

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    Orlando, J. S., Balliet, J. W., Kushnir, A. S., Astor, T. L., Kosz-Vnenchak, M., Rice, S. A., Knipe, D. M., & Schaffer, P. A. (2006). ICP22 is required for wild-type composition and infectivity of herpes simplex virus type 1 virions. Journal of virology, 80(19), 9381-9390. https://doi.org/10.1128/JVI.01061-06