Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8(+) cytotoxic T lymphocytes

The in vivo persistence of gene-modified cells may be limited by the develo pment of a host immune response to vector-encoded proteins. Herpesviruses e vade cytotoxic T-lymphocyte (CTL) recognition by expressing genes which int erfere selectively with presentation of viral antigens by class I major his tocompatibility complex (MHC) molecules. Here, we studied the use of retrov iral vectors encoding herpes simplex virus ICP47, human cytomegalovirus (HC MV) US3, or HCMV US11 to decrease presentation of viral proteins and transg ene products to CD8(+) CTL. Human fibroblasts and T cells transduced to exp ress the ICP47, US3, or US11 genes alone exhibited a decrease in cell surfa ce class I MHC expression. The combination of ICP47 and US11 rendered fibro blasts negative for surface class I MHC and allowed a class I MHC-low popul ation of T cells to be sorted by flow cytometry. Fibroblasts and T cells ex pressing both ICP47 and US11 were protected from CTL-mediated lysis and fai led to stimulate specific memory T-cell responses to transgene products in vitro. Our findings suggest that expression of immunoregulatory viral gene products could be a potential strategy to prolong transgene expression in v ivo.