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Journal of Virology, November 2008, p. 11167-11180, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01218-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Temporal Dynamics of Cytomegalovirus Chromatin Assembly in Productively Infected Human Cells{triangledown}

Alexandra Nitzsche, Christina Paulus,{dagger} and Michael Nevels{dagger}*

Institute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany

Received 12 June 2008/ Accepted 2 September 2008

The genomes of herpesviruses, including human cytomegalovirus (CMV), are double-stranded DNA molecules maintained as episomes during infection. The viral DNA lacks histones when encapsidated in the virion. However, it has been found histone associated inside infected cells, implying unidentified chromatin assembly mechanisms. Our results indicate that components of the host cell nucleosome deposition machinery target intranuclear CMV DNA, resulting in stepwise viral-chromatin assembly. CMV genomes undergo limited histone association and nucleosome assembly as early as 30 min after infection via DNA replication-independent mechanisms. Low average viral-genome chromatinization is maintained throughout the early stages of infection. The late phase of infection is characterized by a striking increase in average histone occupancy coupled with the process of viral-DNA replication. While the initial chromatinization affected all analyzed parts of the CMV chromosome, a subset of viral genomic regions, including the major immediate-early promoter, proved to be largely resistant to replication-dependent histone deposition. Finally, our results predict the likely requirement for an unanticipated chromatin disassembly process that enables packaging of histone-free DNA into progeny capsids.

* Corresponding author. Mailing address: Institute for Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Phone: 49 941 944 4640. Fax: 49 941 944 4641. E-mail: michael.nevels{at}klinik.uni-regensburg.de

{triangledown} Published ahead of print on 10 September 2008.

{dagger} C.P. and M.N. contributed equally to this work.

Journal of Virology, November 2008, p. 11167-11180, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01218-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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