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Title: ICP27-dependent resistance of herpes simplex virus type 1 to leptomycin B is associated with enhanced nuclear localization of ICP4 and ICP0

It was previously shown that herpes simplex virus type 1 (HSV-1) is sensitive to leptomycin B (LMB), an inhibitor of nuclear export factor CRM1, and that a single methionine to threonine change at residue 50 (M50T) of viral immediate-early (IE) protein ICP27 can confer LMB resistance. In this work, we show that deletion of residues 21-63 from ICP27 can also confer LMB resistance. We further show that neither the M50T mutation nor the presence of LMB affects the nuclear shuttling activity of ICP27, suggesting that another function of ICP27 determines LMB resistance. A possible clue to this function emerged when it was discovered that LMB treatment of HSV-1-infected cells dramatically enhances the cytoplasmic accumulation of two other IE proteins, ICP0 and ICP4. This effect is completely dependent on ICP27 and is reversed in cells infected with LMB-resistant mutants. Moreover, LMB-resistant mutations in ICP27 enhance the nuclear localization of ICP0 and ICP4 even in the absence of LMB, and this effect can be discerned in transfected cells. Thus, the same amino (N)-terminal region of ICP27 that determines sensitivity to LMB also enhances ICP27's previously documented ability to promote the cytoplasmic accumulation of ICP4 and ICP0. We speculate that ICP27's effects onmore » ICP4 and ICP0 may contribute to HSV-1 LMB sensitivity.« less
Authors:
 [1] ;  [1] ;  [1] ;  [2]
  1. Department of Microbiology, University of Minnesota Medical School, Mayo Mail Code 196, 420 Delaware St. S.E., Minneapolis, MN 55455 (United States)
  2. Department of Microbiology, University of Minnesota Medical School, Mayo Mail Code 196, 420 Delaware St. S.E., Minneapolis, MN 55455 (United States). E-mail: ricex019@umn.edu
Publication Date:
OSTI Identifier:
20850552
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 352; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2006.04.044; PII: S0042-6822(06)00291-1; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; HERPES SIMPLEX; METHIONINE; MUTANTS; MUTATIONS; PROTEINS; SENSITIVITY; THREONINE; VIRAL DISEASES; VIRUSES