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J. Biol. Chem., Vol. 280, Issue 39, 33357-33367, September 30, 2005

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Cellular p32 Recruits Cytomegalovirus Kinase pUL97 to Redistribute the Nuclear Lamina^*

From the Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Erlangen 91054, Germany

Replication of human cytomegalovirus is limited at the level of nucleocytoplasmic transport of viral capsids, a process that requires the disassembly of the nuclear lamina. Deletion of the protein kinase gene UL97 from the viral genome showed that the activity of pUL97 plays an important role for viral capsid egress. Here, we report that p32, a novel cellular interactor of the viral kinase pUL97, promotes the accumulation of pUL97 at the nuclear membrane by recruiting the p32-pUL97 complex to the lamin B receptor. Transfection of active pUL97, but not a catalytically inactive mutant, induced a redistribution of lamina components as demonstrated for recombinant lamin B receptor-green fluorescent protein and endogenous lamins A and C. Consistent with this, p32 itself and lamins were phosphorylated by pUL97. Importantly, overexpression of p32 in human cytomegalovirus-infected cells resulted in increased efficiency of viral replication and release of viral particles. Thus, it is highly suggestive that the cellular protein p32 recruits pUL97 to induce a dissolution of the nuclear lamina thereby facilitating the nuclear export of viral capsids.

Received for publication, March 10, 2005 , and in revised form, June 8, 2005.

^* This work was supported by the Bayerische Forschungsstiftung Grants 576/03 and 0312654 from the Interdisziplinäres Zentrum für Klinische Forschung, Erlangen, Deutsche Forschungsgemeinschaft Grant SFB473, and the Wilhelm Sander Stiftung Grant 2004.057.1. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Schlossgarten 4, Erlangen 91054, Germany. Tel.: 49-9131-85-26089 (office); 49-9131-85-22100 (laboratory); Fax: 49-9131-85-26493; E-mail: manfred.marschall{at}viro.med.uni-erlangen.de.

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