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

Joy Lengyel, Anna K. Strain, Keith D. Perkins, Stephen A Rice

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 on ICP4 and ICP0 may contribute to HSV-1 LMB sensitivity.

Original languageEnglish (US)
Pages (from-to)368-379
Number of pages12
JournalVirology
Volume352
Issue number2
DOIs
StatePublished - Sep 1 2006

Bibliographical note

Funding Information:
We are grateful to Minoru Yoshida for the gift of LMB and to Leslie Schiff for many helpful discussions. We also acknowledge Steve Bachenheimer for generously communicating unpublished results. This research was supported by a grant from the NIH (R01-AI42737). Anna Strain was supported by a fellowship from the Minnesota Craniofacial Research Training (Minncrest) Program (NIH award T32-DE007288).

Keywords

  • Herpes simplex virus 1 (HSV-1)
  • ICP0
  • ICP27
  • ICP4
  • Leptomycin B
  • Nuclear export
  • Resistance

Fingerprint Dive into the research topics of 'ICP27-dependent resistance of herpes simplex virus type 1 to leptomycin B is associated with enhanced nuclear localization of ICP4 and ICP0'. Together they form a unique fingerprint.

Cite this