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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-05-1504.

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Blood, 15 June 2003, Vol. 101, No. 12, pp. 4870-4877

IMMUNOBIOLOGY

Human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR {alpha}-chain

Jenny Odeberg, Bodo Plachter, Lars Brandén, and Cecilia Söderberg-Nauclér

From the Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Institute for Virology, University of Mainz, Germany; and Karolinska Institutet, Clinical Research Center (CRC), Huddinge, Sweden.

Human cytomegalovirus (HCMV) has developed multiple strategies to escape immune recognition. Here, we demonstrate that HCMV down-regulates HLA-DR expression in infected interferon {gamma} (IFN-{gamma})–stimulated fibroblasts at 1 day after infection. Decreased HLA-DR expression was not observed on cells infected with an HCMV strain lacking the pp65 gene (RVAD65), but was observed on cells transfected with the pp65 gene. HLA-DR expression accumulated in vacuoles near the nucleus in HCMV-infected, but not in uninfected or RVAD65-infected cells. In addition, the HLA-DR {alpha}-chain, but not the {beta}-chain or HLA-DM, was degraded in HCMV-infected but not in RVAD65-infected cells. Thus, the HCMV protein pp65 mediates decreased expression of HLA-DR, by mediating an accumulation of HLA class II molecules in lysosomes that results in degradation of the HLA-DR {alpha}-chain.


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