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

Abstract

Previously we have shown that pseudorabies virus (PrV) down-regulates the expression of porcine MHC class I molecules by interfering with the transporter associated with antigen processing (TAP). During lytic PrV infection, the half-lives of both host and viral mRNA are regulated by the product of virion host shut-off (vhs) gene, UL41. PrV vhs protein induces degradation of cellular mRNA including those encoding class I and TAP. Therefore, further elucidation of specific mechanisms of down-regulation of class I molecules by PrV necessitates construction of a vhs deletion mutant. Two such mutants (vhsDelta1 and vhsDelta2) were generated by homologous recombination between the wild type (wt) PrV Indiana-F strain, and plasmids containing truncated UL41 gene of PrV into which the enhanced green fluorescent protein (EGFP) cassette was inserted. Compared with the wt virus, both the vhs mutants exhibited slower in vitro growth kinetics. The mutants, like the wt virus, inhibited the peptide transport activity of TAP and down-regulated cell surface expression of class I molecules. These findings suggest that, inhibition of TAP activity in PrV-infected cells is due to mechanism(s) specifically directed at class I pathway and not due to the non-specific vhs activity of the virus.