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Journal of Virology, March 2008, p. 2065-2078, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01967-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Essential Human Cytomegalovirus Gene UL52 Is Required for Cleavage-Packaging of the Viral Genome{triangledown}

Eva Maria Borst, Karen Wagner, Anne Binz, Beate Sodeik, and Martin Messerle*

Department of Virology, Hannover Medical School, 30625 Hannover, Germany

Received 7 September 2007/ Accepted 3 December 2007

Replication of human cytomegalovirus (HCMV) produces large DNA concatemers of head-to-tail-linked viral genomes that upon packaging into capsids are cut into unit-length genomes. The mechanisms underlying cleavage-packaging and the subsequent steps prior to nuclear egress of DNA-filled capsids are incompletely understood. The hitherto uncharacterized product of the essential HCMV UL52 gene was proposed to participate in these processes. To investigate the function of pUL52, we constructed a {Delta}UL52 mutant as well as a complementing cell line. We found that replication of viral DNA was not impaired in noncomplementing cells infected with the {Delta}UL52 virus, but viral concatemers remained uncleaved. Since the subnuclear localization of the known cleavage-packaging proteins pUL56, pUL89, and pUL104 was unchanged in {Delta}UL52-infected fibroblasts, pUL52 does not seem to act via these proteins. Electron microscopy studies revealed only B capsids in the nuclei of {Delta}UL52-infected cells, indicating that the mutant virus has a defect in encapsidation of viral DNA. Generation of recombinant HCMV genomes encoding epitope-tagged pUL52 versions showed that only the N-terminally tagged pUL52 supported viral growth, suggesting that the C terminus is crucial for its function. pUL52 was expressed as a 75-kDa protein with true late kinetics. It localized preferentially to the nuclei of infected cells and was found to enclose the replication compartments. Taken together, our results demonstrate an essential role for pUL52 in cleavage-packaging of HCMV DNA. Given its unique subnuclear localization, the function of pUL52 might be distinct from that of other cleavage-packaging proteins.

* Corresponding author. Mailing address: Hannover Medical School, Department of Virology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Phone: 49-511-5324320. Fax: 49-511-5328736. E-mail: messerle.martin{at}mh-hannover.de

{triangledown} Published ahead of print on 12 December 2007.

Journal of Virology, March 2008, p. 2065-2078, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01967-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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