Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8(+) cytotoxic T lymphocytes
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Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8(+) cytotoxic T lymphocytes. / Berger, C; Xuereb, S; Johnson, D C; Watanabe, K S; Kiem, H P; Greenberg, P D; Riddell, S R.
In: J VIROL, Vol. 74, No. 10, 05.2000, p. 4465-73.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8(+) cytotoxic T lymphocytes
AU - Berger, C
AU - Xuereb, S
AU - Johnson, D C
AU - Watanabe, K S
AU - Kiem, H P
AU - Greenberg, P D
AU - Riddell, S R
PY - 2000/5
Y1 - 2000/5
N2 - 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.
AB - 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.
KW - Animals
KW - Antigen Presentation
KW - Cells, Cultured
KW - Cytomegalovirus/genetics
KW - Cytotoxicity, Immunologic
KW - Fibroblasts/metabolism
KW - Gene Expression
KW - Genetic Vectors
KW - Glycoproteins
KW - Herpesviridae/genetics
KW - Humans
KW - Immediate-Early Proteins/genetics
KW - Killer Cells, Natural/immunology
KW - Lymphocyte Activation
KW - Membrane Proteins
KW - Mice
KW - Phosphotransferases (Alcohol Group Acceptor)/genetics
KW - RNA-Binding Proteins/genetics
KW - Recombinant Proteins/immunology
KW - Retroviridae/genetics
KW - T-Lymphocytes, Cytotoxic/immunology
KW - Transgenes
KW - Viral Proteins/genetics
U2 - 10.1128/jvi.74.10.4465-4473.2000
DO - 10.1128/jvi.74.10.4465-4473.2000
M3 - SCORING: Journal article
C2 - 10775582
VL - 74
SP - 4465
EP - 4473
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 10
ER -