Cells present peptides on class I major histocompatibility complex (MHC class I) molecules to cytotoxic CD8+ T lymphocytes (CTL), which recognize viral peptides and destroy infected cells. Many viruses encode proteins that inhibit the antigen presentation pathway. Here we demonstrate that feline herpesvirus 1 infection of cat fibroblasts effectively blocks MHC class I surface expression by blocking the TAP peptide transporter. Based on previous publications that varicellovirus UL49.5 is an immune evasion gene, we cloned UL49.5 from FHV-1 and demonstrated that this gene is sufficient to block MHC class I antigen presentation. As well as being a common pathogen of cats, FHV1 is a relatively convenient model for viral pathogenesis. Using a two-step homologous recombination technique, we have constructed a knockout virus lacking UL49.5 expression. Feline cells infected with the mutant virus show similar MHC class I surface expression as the uninfected controls. As well as offering a potential approach to varicellovirus vaccination, these studies give greater understanding of viral immune evasion and pathogenesis, as well as of the mechanism of MHC class I antigen processing and presentation.
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