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

Submitted May 22, 2002
Accepted January 23, 2003
The human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR -chain
Jenny Odeberg, Bodo Plachter, Lars Branden, and Cecilia Soderberg-Naucler*
Departent of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
Institute for Virology, University of Mainz, Mainz, Germany
Clinical Research Center (CRC), Karolinska Institutet, Huddinge, Sweden
* Corresponding author; email: cecilia.soderberg.naucler{at}cmm.ki.se.
Human cytomegalovirus (HCMV) has developed multiple strategies to escape immune recognition. Here, we demonstrate that HCMV downregulates HLA-DR expression in infected IFN- stimulated fibroblasts at 1 day post infection. Decreased HLA-DR expression was not observed in cells infected with an HCMV strain lacking the pp65 gene (RVAD65), but in 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 -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 lysosmes that results in degradation of the HLA-DR- chain.

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