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Murine Cytomegalovirus Abortively Infects Human Dendritic Cells, Leading to Expression and Presentation of Virally Vectored Genes

Xiuqing Wang,^1, Martin Messerle,² Ramil Sapinoro,¹ Kathlyn Santos,¹ Peter K. Hocknell,^1, Xia Jin,³ and Stephen Dewhurst^1,4*

Departments of Microbiology and Immunology,¹ Medicine,³ Cancer Center, University of Rochester Medical Center, Rochester, New York 14642,⁴ Virus-Cell Interaction Group, Medical Faculty, University of Halle-Wittenberg, Halle 06120, Germany²

Received 25 February 2003/ Accepted 2 April 2003

Dendritic cells (DC) are potent antigen-presenting cells that play a crucial role in antigen-specific immune responses. Thus, the targeting of exogenous antigens to DC has become a popular approach for cancer immunotherapy and vaccine development. In this report, we studied the interplay between murine cytomegalovirus (MCMV) and human monocyte-derived DC. The results showed that an enhanced green fluorescent protein (EGFP)-encoding, replication-competent MCMV vector underwent abortive infection in human DC; this was accompanied by the efficient expression of EGFP. Infection of human DC by this vector resulted in a modest increase in the expression of cell surface proteins associated with DC maturation and has no significant effect on the immunostimulatory function of the cells, as reflected by their ability to support T-cell proliferation in a mixed-lymphocyte reaction. Finally, an MCMV vector encoding the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein was constructed and used to infect cultured human DC. The infected DC were shown to be capable of stimulating the expansion of autologous, gp120-specific, class I-restricted T lymphocytes from an HIV-1-negative donor, as determined by tetramer staining and enzyme-linked immunospot analysis. Taken together, these results suggest that MCMV may have potential utility as a vector for human vaccine development.

Present address: Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007.

Present address: Transkaryotic Therapies, Inc., Cambridge, MA 02139.

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