Journal
JOURNAL OF VIROLOGY
Volume 74, Issue 10, Pages 4465-4473Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.74.10.4465-4473.2000
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Funding
- NCI NIH HHS [CA18029, P01 CA018029] Funding Source: Medline
- NEI NIH HHS [R01 EY011245] Funding Source: Medline
- NIAID NIH HHS [AI41754, AI43650] Funding Source: Medline
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The in vivo persistence of gene-modified cells may be limited by the development of a host immune response to vector-encoded proteins. Herpesviruses evade cytotoxic T-lymphocyte (CTL) recognition by expressing genes which interfere selectively with presentation of viral antigens by class I major histocompatibility complex (MHC) molecules. Here, we studied the use of retroviral vectors encoding herpes simplex virus ICP47, human cytomegalovirus (HCMV) US3, or HCMV US11 to decrease presentation of viral proteins and transgene products to CD8(+) CTL. Human fibroblasts and T cells transduced to express the ICP47, US3, or US11 genes alone exhibited a decrease in cell surface class I MHC expression. The combination of ICP47 and US11 rendered fibroblasts negative for surface class I MHC and allowed a class I MHC-low population of T cells to be sorted by flow cytometry. Fibroblasts and T cells expressing both ICP47 and US11 were protected from CTL-mediated lysis and failed 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 vivo.
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