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Journal of Virology, July 2004, p. 7803-7812, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7803-7812.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral Replication

Michael Nevels,{dagger} Wolfram Brune,{ddagger} and Thomas Shenk*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014

Received 5 November 2003/ Accepted 6 April 2004

The 72-kDa immediate-early 1 protein (IE1-72kDa) of human cytomegalovirus has been previously shown to be posttranslationally modified by covalent conjugation to the ubiquitin-related protein SUMO-1. Using an infectious bacterial artificial chromosome clone of human cytomegalovirus, we constructed a mutant virus (BADpmIE1-K450R) that is deficient for SUMOylation of IE1-72kDa due to a single amino acid exchange in the SUMO-1 attachment site. Compared to wild-type virus, this mutant grew more slowly and generated a reduced yield in infected human fibroblasts, indicating that SUMO modification is required for the full activity of IE1-72kDa. The lack of SUMOylation did not affect the intranuclear localization of IE1-72kDa, including its ability to target to and disrupt PML bodies and to bind to mitotic chromatin. Likewise, SUMOylation-deficient IE1-72kDa activated several viral promoters as efficiently as the wild-type protein. However, the failure to modify IE1-72kDa resulted in substantially reduced levels of the IE2 transcript and its 86-kDa protein (IE2-86kDa). These observations suggest that SUMO modification of IE1-72kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86kDa.

* Corresponding author. Mailing address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014. Phone: (609) 258-5992. Fax: (609) 258-1704. E-mail: tshenk{at}princeton.edu.

{dagger} Present address: Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Forschungszentrum (FZL), D-93047 Regensburg, Germany.

{ddagger} Present address: Rudolf-Virchow-Zentrum für Experimentelle Biomedizin, Universität Würzburg, D-97078 Würzburg, Germany.

Journal of Virology, July 2004, p. 7803-7812, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7803-7812.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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