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Journal of Virology, May 2000, p. 4465-4473, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Expression of Herpes Simplex Virus ICP47 and Human Cytomegalovirus US11 Prevents Recognition of Transgene Products by CD8+ Cytotoxic T Lymphocytes

Carolina Berger,1 Suzanne Xuereb,1 David C. Johnson,2 Kathe S. Watanabe,3 Hans-Peter Kiem,1,3 Philip D. Greenberg,1,3,4 and Stanley R. Riddell1,3,*

Fred Hutchinson Cancer Research Center, Seattle, Washington 981091; Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 972012; and Department of Medicine3 and Department of Immunology,4 University of Washington, Seattle, Washington 98195

Received 16 September 1999/Accepted 17 February 2000

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.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3-100, Seattle, WA 98109-1024. Phone: (206) 667-5249. Fax: (206) 667-7983. E-mail: sriddell{at}fhcrc.org.

Journal of Virology, May 2000, p. 4465-4473, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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