Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway

M D Koffa1, J B Clements, E Izaurralde

  • 1Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.

The EMBO Journal
|October 13, 2001
PubMed

Insights

Herpes simplex virus ICP27 protein enhances viral mRNA export by interacting with cellular export factors REF and TAP/NXF1. This novel mechanism bypasses the CRM1 pathway, facilitating efficient viral gene expression.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • Herpes simplex virus (HSV) requires efficient mRNA export for replication.
  • The precise mechanism of viral mRNA export mediated by HSV ICP27 protein is not fully understood.

Purpose of the Study:

  • To elucidate the role and mechanism of HSV ICP27 protein in mRNA export.
  • To determine the cellular factors and pathways involved in ICP27-mediated viral mRNA export.

Main Methods:

  • Microinjection of ICP27 protein into Xenopus laevis oocytes.
  • Use of specific inhibitors to probe export pathways.
  • In vitro binding assays and analysis of infected cells.

Main Results:

  • ICP27 protein significantly stimulates the export of intronless viral mRNAs, but not cellular mRNAs, U snRNAs, or tRNA.
  • ICP27 does not utilize the CRM1 pathway for viral mRNA export.
  • ICP27-mediated export requires REF and TAP/NXF1, key factors in cellular mRNA export.
  • ICP27 directly binds to REF, forming complexes with TAP/NXF1 in vitro and in infected cells.
  • A mutant ICP27 unable to bind REF fails to promote viral mRNA export.

Conclusions:

  • ICP27 protein hijacks the cellular mRNA export machinery, specifically the REF-TAP/NXF1 pathway, for viral mRNA export.
  • This interaction facilitates the export of viral mRNAs that are otherwise poorly exported.
  • A novel mechanism for viral mRNA export involving direct recruitment of cellular export factors by a viral protein is proposed.

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