Open AccessExpression of Herpes Simplex Virus ICP47 and Human Cytomegalovirus US11 Prevents Recognition of Transgene Products by CD8+Cytotoxic T Lymphocytes
Author(s) -
Carolina Berger,
Suzanne M. Xuereb,
David C. Johnson,
Kathe S. Watanabe,
Hans Peter Kiem,
Philip D. Greenberg,
Stanley R. Riddell
Publication year - 2000
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.74.10.4465-4473.2000
Subject(s) - biology , cytotoxic t cell , mhc class i , ctl* , herpes simplex virus , major histocompatibility complex , virology , cd8 , antigen presentation , transgene , immune system , immunology , virus , gene , in vitro , genetics
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.