Effects of virion host shut-off activity of bovine herpesvirus 1 on MHC class I expression

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Bovine herpesvirus 1 (BHV-1) down-regulates major histocompatibility complex (MHC) class I molecules.
• BHV-1 interferes with peptide transport via the transporter associated with antigen processing (TAP).
• BHV-1 also reduces mRNA expression for MHC class I and other cellular proteins.

Purpose of the Study:

• To elucidate the mechanisms by which BHV-1 down-regulates MHC class I molecules.
• To investigate the role of the virion host shut-off (vhs) protein in this process.

Main Methods:

• Generation of a BHV-1 virion host shut-off (vhs) deletion mutant.
• Analysis of peptide transport by the transporter associated with antigen processing (TAP).
• Assessment of cell surface expression and synthesis of MHC class I molecules.

Main Results:

• The vhs deletion mutant, like wildtype BHV-1, interfered with TAP function and reduced cell surface MHC class I expression.
• Unlike wildtype BHV-1, the vhs deletion mutant did not impair the synthesis of MHC class I molecules.
• These findings indicate dual mechanisms for MHC class I down-regulation by BHV-1: vhs activity and specific MHC class I pathway interference.

Conclusions:

• BHV-1 down-regulation of MHC class I molecules is mediated by both vhs activity and other virus-specific mechanisms.
• A BHV-1 vhs deletion mutant is expected to have reduced pathogenicity and enhanced immunogenicity.
• The vhs deletion mutant represents a promising candidate for a safer and more effective BHV-1 vaccine.