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Journal of Virology, April 2006, p. 3863-3871, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3863-3871.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inactivating a Cellular Intrinsic Immune Defense Mediated by Daxx Is the Mechanism through Which the Human Cytomegalovirus pp71 Protein Stimulates Viral Immediate-Early Gene Expression

Ryan T. Saffert and Robert F. Kalejta*

Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin—Madison, 1525 Linden Drive, Madison, Wisconsin 53706

Received 30 November 2005/ Accepted 27 January 2006

Human cytomegalovirus (HCMV) masterfully evades adaptive and innate immune responses, allowing infection to be maintained and periodically reactivated for the life of the host. Here we show that cells also possess an intrinsic immune defense against HCMV that is disarmed by the virus. In HCMV-infected cells, the promyelocytic leukemia nuclear body (PML-NB) protein Daxx silences viral immediate-early gene expression through the action of a histone deacetylase. However, this antiviral tactic is efficiently neutralized by the viral pp71 protein, which is incorporated into virions, delivered to cells upon infection, and mediates the proteasomal degradation of Daxx. This work demonstrates the mechanism through which pp71 activates viral immediate-early gene expression in HCMV-infected cells. Furthermore, it provides insight into how a PML-NB protein institutes an intrinsic immune defense against a DNA virus and how HCMV pp71 inactivates this defense.

* Corresponding author. Mailing address: Institute for Molecular Virology, University of Wisconsin—Madison, 1525 Linden Drive, Madison, WI 53706. Phone: (608) 265-5546. Fax: (608) 262-7414. E-mail: rfkalejta{at}wisc.edu.

Journal of Virology, April 2006, p. 3863-3871, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3863-3871.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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