This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dahl, J.
Right arrow Articles by Benjamin, T. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dahl, J.
Right arrow Articles by Benjamin, T. L.

 Previous Article  |  Next Article 

Journal of Virology, September 2007, p. 10064-10071, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00821-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Polyomavirus Small T Antigen Controls Viral Chromatin Modifications through Effects on Kinetics of Virus Growth and Cell Cycle Progression{triangledown}

Jean Dahl, H. Isaac Chen, Michael George, and Thomas L. Benjamin*

Department of Pathology, Harvard Medical School, Boston, Massachusetts

Received 17 April 2007/ Accepted 29 June 2007

Minichromosomes of wild-type polyomavirus were previously shown to be highly acetylated on histones H3 and H4 compared either to bulk cell chromatin or to viral chromatin of nontransforming hr-t mutants, which are defective in both the small T and middle T antigens. A series of site-directed virus mutants have been used along with antibodies to sites of histone modifications to further investigate the state of viral chromatin and its dependence on the T antigens. Small T but not middle T was important in hyperacetylation at major sites in H3 and H4. Mutants blocked in middle T signaling pathways but encoding normal small T showed a hyperacetylated pattern similar to that of wild-type virus. The hyperacetylation defect of hr-t mutant NG59 was partially complemented by growth of the mutant in cells expressing wild-type small T. In contrast to the hypoacetylated state of NG59, NG59 minichromosomes were hypermethylated at specific lysines in H3 and also showed a higher level of phosphorylation at H3ser10, a modification associated with the late G2 and M phases of the cell cycle. Comparisons of virus growth kinetics and cell cycle progression in wild-type- and NG59-infected cells showed a correlation between the phase of the cell cycle at which virus assembly occurred and histone modifications in the progeny virus. Replication and assembly of wild-type virus were completed largely during S phase. Growth of NG59 was delayed by about 12 h with assembly occurring predominately in G2. These results suggest that small T affects modifications of viral chromatin by altering the temporal coordination of virus growth and the cell cycle.

* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA 02115. Phone: (617) 432-1060. Fax: (617) 432-2689. E-mail: Thomas_benjamin{at}hms.harvard.edu

{triangledown} Published ahead of print on 11 July 2007.

Journal of Virology, September 2007, p. 10064-10071, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00821-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»