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Journal of Virology, May 2008, p. 4308-4319, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.01447-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inhibition of CD1 Antigen Presentation by Human Cytomegalovirus{triangledown}

Martin J. Raftery,1* Manuel Hitzler,1 Florian Winau,2 Thomas Giese,3 Bodo Plachter,4 Stefan H. E. Kaufmann,2 and Günther Schönrich1

Institute of Virology, Charité Medical School, Chariteplatz 1, D-10117 Berlin, Germany,1 Max-Planck-Institute for Infection Biology, Chariteplatz 1, D-10117 Berlin, Germany,2 Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany,3 Institute of Virology, University of Mainz, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany4

Received 3 July 2007/ Accepted 6 February 2008

The betaherpesvirus human cytomegalovirus (HCMV) encodes several molecules that block antigen presentation by the major histocompatibility complex (MHC) proteins. Humans also possess one other family of antigen-presenting molecules, the CD1 family; however, the effect of HCMV on CD1 expression is unknown. The majority of CD1 molecules are classified on the basis of homology as group 1 CD1 and are present almost exclusively on professional antigen-presenting cells such as dendritic cells, which are a major target for HCMV infection and latency. We have determined that HCMV encodes multiple blocking strategies targeting group 1 CD1 molecules. CD1 transcription is strongly inhibited by the HCMV interleukin-10 homologue cmvIL-10. HCMV also blocks CD1 antigen presentation posttranscriptionally by the inhibition of CD1 localization to the cell surface. This function is not performed by a known HCMV MHC class I-blocking molecule and is substantially stronger than the blockage induced by herpes simplex virus type 1. Antigen presentation by CD1 is important for the development of the antiviral immune response and the generation of mature antigen-presenting cells. HCMV present in antigen-presenting cells thus blunts the immune response by the blockage of CD1 molecules.

* Corresponding author. Mailing address: Institute of Virology, Charité Medical School, Chariteplatz 1, D-10117 Berlin, Germany. Phone: 49-30-450-525071. Fax: 49-30-450-525907. E-mail: martin.raftery{at}charite.de

{triangledown} Published ahead of print on 20 February 2008.

Journal of Virology, May 2008, p. 4308-4319, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.01447-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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