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Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing

H E Bryant1, S E Wadd, A I Lamond

  • 1Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom.

Journal of Virology
|April 5, 2001
PubMed

Insights

Herpes simplex virus type 1 (HSV-1) protein IE63 interacts with splicing factor SAP145, inhibiting pre-mRNA processing. This interaction, crucial for viral infection, impacts spliceosome complex formation and function.

Area of Science:

  • Molecular Virology
  • RNA Biology
  • Cellular Microbiology

Background:

  • Herpes simplex virus type 1 (HSV-1) infection involves complex interactions between viral proteins and host cellular machinery.
  • The viral protein IE63 (ICP27) is known to be multifunctional and plays a significant role in modulating host cell processes.
  • Pre-mRNA splicing is a fundamental cellular process essential for gene expression, and its dysregulation can impact viral replication.

Purpose of the Study:

  • To investigate the interaction between HSV-1 IE63 protein and the pre-mRNA splicing factor SAP145.
  • To elucidate the functional consequences of this interaction on the pre-mRNA splicing process during HSV-1 infection.
  • To understand the role of IE63 in modulating host cell splicing machinery for viral benefit.

Main Methods:

  • Co-immunoprecipitation assays to detect the interaction between IE63 and SAP145.
  • Analysis of viral mutants with specific mutations in IE63 homology domains.
  • In vitro splicing assays to assess the impact of IE63 on splicing efficiency and spliceosome complex formation.
  • Western blotting and gel mobility shift assays to analyze spliceosome complex composition.

Main Results:

  • HSV-1 IE63 directly interacts with the essential splicing factor SAP145, and they colocalize in infected cells.
  • Mutations in IE63's KH and Sm homology domains disrupt this interaction and impair viral host shutoff and splicing inhibition.
  • IE63 inhibits in vitro splicing prior to the first catalytic step and alters the B/C spliceosome complex formation.
  • Both IE63 and SAP145 are found within the B/C complex, indicating their interaction within this functional unit to impede splicing progression.

Conclusions:

  • The interaction between HSV-1 IE63 and SAP145 is critical for IE63's ability to inhibit pre-mRNA splicing.
  • IE63 likely manipulates the spliceosome, specifically the B/C complex, to alter host and viral RNA processing.
  • This modulation of splicing by IE63 may facilitate the efficient export of viral transcripts, contributing to successful HSV-1 infection.

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