Inhibition of TAP by pseudorabies virus is independent of its vhs activity

Aruna P N Ambagala1, Raju S Gopinath, S Srikumaran

  • 1Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Nebraska-Lincoln, NE 68583-0905, USA.

Virus Research
|September 3, 2003
PubMed

Insights

Pseudorabies virus (PrV) infection down-regulates porcine MHC class I molecules. A vhs deletion mutant confirmed this is not due to non-specific vhs activity, but a mechanism targeting the class I pathway.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Pseudorabies virus (PrV) down-regulates porcine MHC class I expression by interfering with the transporter associated with antigen processing (TAP).
  • The PrV virion host shut-off (vhs) protein, encoded by UL41, regulates mRNA half-lives and degrades cellular mRNA, including that for MHC class I and TAP.

Purpose of the Study:

  • To elucidate the specific mechanisms by which PrV down-regulates MHC class I molecules.
  • To investigate the role of the vhs protein in this down-regulation process.

Main Methods:

  • Construction of two vhs deletion mutants (vhsDelta1 and vhsDelta2) of wild-type PrV Indiana-F using homologous recombination.
  • Insertion of an enhanced green fluorescent protein (EGFP) cassette into truncated UL41 gene plasmids.
  • Comparison of mutant and wild-type virus growth kinetics, TAP peptide transport activity, and cell surface MHC class I expression.

Main Results:

  • The vhs deletion mutants exhibited slower in vitro growth kinetics compared to the wild-type virus.
  • Both vhs mutants and the wild-type virus inhibited TAP peptide transport activity.
  • Both vhs mutants and the wild-type virus down-regulated cell surface expression of MHC class I molecules.

Conclusions:

  • The inhibition of TAP activity and down-regulation of MHC class I molecules in PrV-infected cells are mediated by mechanisms specifically targeting the class I pathway.
  • These effects are not attributable to the non-specific mRNA degradation activity of the PrV vhs protein.

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